phenanthrenes and Asthma

Air pollutants such as diesel exhaust particles (DEP) are thought to cause pulmonary diseases such as asthma as a result of oxidative stress. While DEP contain a large number of polycyclic aromatic hydrocarbons, we have focused on 9,10-phenanthrenequinone (9,10-PQ) and 1,2-naphthoquinone (1,2-NQ) because of their chemical properties based on their oxidative and chemical modification capabilities. We have found that 9,10-PQ interacts with electron donors such as NADPH (in the presence of enzymes) and dithiols, resulting in generation of excess reactive oxygen species (ROS) through redox cycling. We have also shown that 1,2-NQ is able to modify protein thiols, leading to protein adducts associated with activation of redox signal transduction pathways at lower concentrations and toxicity at higher concentrations. In this review, we briefly introduce our findings from the last two decades.

Topics: Air Pollutants; Antioxidant Response Elements; Asthma; NADP; Naphthoquinones; Oxidation-Reduction; Oxidative Stress; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Reactive Oxygen Species; Signal Transduction; Sulfhydryl Compounds; Vehicle Emissions

To investigate the therapeutic mechanism of Tripterygium polyglucoside (TII) in treating asthma patients.. Thirty asthma patients of middle or sever leoel were selected and randomly divided into three groups, Group A treated with TII, Group B treated with prednisone and Group C, the control group. Their peripheral CD4+, CD8+ T-lymphocytes were counted by flow cytometer and serum interleukin-5 (IL-5) level determined by ELISA before and after 4 weeks' treatment.. In Group A, after treatment, CD4+ T-lymphocytes reduced from 0.462 +/- 0.035 to 0.426 +/- 0.039 (P < 0.01), CD8+ increased from 0.201 +/- 0.045 to 0.253 +/- 0.043 (P < 0.01), and serum IL-5 median concentration reduced from 65.3 ng/L to 10.9 ng/L (P < 0.01). Similar results was revealed in Group B, while there was insignificant change of the parameters in Group C. The serum concentration of IL-5 was positively correlated with the peripheral CD4+ count (r = 0.61, P < 0.01).. TII is highly effective in treating asthma through regulating T-lymphocyte subset disorder and inhibiting production of IL-5.

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Asthma; CD4-CD8 Ratio; Diterpenes; Drugs, Chinese Herbal; Epoxy Compounds; Female; Glucosides; Humans; Immunosuppressive Agents; Interleukin-5; Male; Middle Aged; Phenanthrenes; Phytotherapy; T-Lymphocyte Subsets; Tripterygium

Semi-volatile organic compounds (SVOCs) are a major global problem that causes the greatest impact on urban settings and have been linked to bronchial asthma in both children and adults in Pakistan. The association between exposure of polycyclic aromatic hydrocarbons (PAHs) and asthma in the adult population is less clear. The current study aimed to assess the clinico-chemical parameters and blood levels of naphthalene phenanthrene, pyrene, and 1,2-benzanthracene and urinary levels of 1-OH pyrene and 1-OH phenanthrene as well as asthma-related biomarkers immunoglobulin E (IgE), resistin, and superoxide dismutase (SOD) of oxidative stress and other hematologic parameters in adults and their relationship with bronchial asthma. The GC/MS analysis showed higher mean concentrations of blood PAHs in asthma respondents (4.48 ± 1.34, 3.46 ± 1.04, 0.10 ± 0.03, and 0.29 ± 0.09) (ng/mL) as compared to controls (3.07 ± 0.92, 1.71 ± 0.51, 0.06 ± 0.02, and 0.11 ± 0.03) (ng/mL), with p = .006, p = .001, p = .050, and p = .001. Similarly, urinary levels of 1-OHpyr and 1-OHphe were significantly increased in adults with bronchial asthma (0.54 ± 0.16; 0.13 ± 0.04) (μmol/mol-Cr) than in controls (0.30 ± 0.09; 0.05 ± 0.02) (μmol/mol-Cr), with p = .002 and p = .0001, respectively, with a significant positive correlation to asthma severity. The asthma-related biomarkers IgE, resistin, and SOD were significantly higher (p 0.0001, 0.0001, and 0.0001) in people with asthma than in control persons. The findings showed that higher blood and urine PAHs levels were linked to higher asthma risk in adults and significant interaction with participants who smoked, had allergies, had a family history of asthma, and were exposed to dust. The current study's findings will be useful to local regulatory agencies in Lahore in terms of managing exposure and advocating efforts to minimize PAH pollution and manage health.

Topics: Adult; Asthma; Biomarkers; Child; Humans; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Pyrenes; Resistin; Superoxide Dismutase

This study is to determine the role and mechanism of cryptotanshinone (CTS) in allergic airway inflammation. Asthma induced by OVA was established in BALB/c mice. We found increased airway hyperresponsiveness (AHR), increased inflammatory cell infiltration, elevated levels of TNF-α, interleukin-1β (IL-1β), IL-4, IL-5, IL-6 and IL-13, decreased interferon gamma (IFN-γ) in lung tissue, increased content of total immunoglobulin E (IgE), OVA specific IgE, Eotaxin, ICAM-1, VCAM-1, nuclear factor-kappaB (NF-κB) and phosphorylation of p38 MAPK in lung tissue. However, the administration of CTS significantly decreased AHR in asthmatic mice, reduced inflammation around the bronchioles and inflammatory cells around airway, regulated cytokine production, reduced the total IgE and OVA-specific IgE levels, and inhibited NF-κB activation and p38 MAPK phosphorylation. In vitro experiments in 16 HBE cells revealed that CTS attenuated CAM-1 and IL-6 expression. These results indicate that CTS alleviates allergic airway inflammation by modulating p38 MAPK phosphorylation and NF-κB activation.

Topics: Animals; Asthma; Bronchial Hyperreactivity; Bronchoalveolar Lavage Fluid; Chemotaxis, Leukocyte; Cytokines; Drugs, Chinese Herbal; Female; Hypersensitivity; Immunoglobulin E; Inflammation; Lung; Mice; Mice, Inbred BALB C; NF-kappa B; Ovalbumin; p38 Mitogen-Activated Protein Kinases; Phenanthrenes; Phosphorylation

Abnormal proliferation of airway smooth muscle cells (ASMCs) is a hallmark of airway remodeling. Platelet-derived growth factor (PDGF) is known to be a major stimulus inducing the proliferation of ASMCs. It has been reported that triptolide demonstrates protective effects against airway remodeling. In this study, we investigated the antiproliferative effects of triptolide on PDGF-induced ASMCs and its underlying mechanisms. Cell proliferation was determined using the Cell Counting Kit-8 (CCK-8) assay. Flow cytometry was used to study the influence of triptolide on cell cycle and apoptosis. Quantitative real-time PCR and Western blot analysis were employed to detect the expression of proliferating cell nuclear antigen (PCNA), cyclinD1 and cyclin dependent kinase 4 (CDK4). Proteins involved in the protein kinase B (AKT) and nuclear factor kappa B (NF-κB) signaling pathways were evaluated using Western blot analysis. Triptolide could significantly inhibit cell proliferation, induce cell cycle arrest in the G0/G1 phase, and reduce the expression of PCNA, cyclinD1, and CDK4 in PDGF-treated ASMCs. Levels of phosphorylated AKT, p65 and NF-κB inhibitor α (IκBα) stimulated by the presence of PDGF were markedly suppressed after triptolide treatment. Moreover, triptolide cotreatment with the phosphatidylinositol 3 kinase (PI3k) inhibitor, 2-(4-morpholinyl)-8-phenylchromone (LY294002), could further suppress the proliferation, NF-κB activation and cyclinD1 expression. Similar results were observed after triptolide cotreatment with the NF-κB inhibitor, ammonium pyrrolidinedithiocarbamate (PDTC). Our results suggest that triptolide could inhibit the PDGF-induced proliferation of ASMCs through G0/G1 cell cycle arrest and suppression of the AKT/NF-κB/cyclinD1 signaling pathway.

Topics: Airway Remodeling; Animals; Asthma; Bronchi; Cell Proliferation; Cells, Cultured; Chromones; Cyclin D1; Diterpenes; Epoxy Compounds; G1 Phase Cell Cycle Checkpoints; Humans; Morpholines; Myocytes, Smooth Muscle; NF-kappa B; Phenanthrenes; Phosphatidylinositol 3-Kinases; Phosphorylation; Platelet-Derived Growth Factor; Primary Cell Culture; Proto-Oncogene Proteins c-akt; Pyrrolidines; Rats; Signal Transduction; Thiocarbamates

We have reported that triptolide can inhibit airway remodeling in a murine model of asthma via TGF-β1/Smad signaling. In the present study, we aimed to investigate the effect of triptolide on airway smooth muscle cells (ASMCs) proliferation and the possible mechanism.. Rat airway smooth muscle cells were cultured and made synchronized, then pretreated with different concentration of triptolide before stimulated by TGF-β1. Cell proliferation was evaluated by MTT assay. Flow cytometry was used to study the influence of triptolide on cell cycle and apoptosis. Signal proteins (Smad2, Smad3 and Smad7) were detected by western blotting analysis.. Triptolide significantly inhibited TGF-β1-induced ASMC proliferation (P<0.05). The cell cycle was blocked at G1/S-interphase by triptolide dose dependently. No pro-apoptotic effects were detected under the concentration of triptolide we used. Western blotting analysis showed TGF-β1 induced Smad2 and Smad3 phosphorylation was inhibited by triptolide pretreatment, and the level of Smad7 was increased by triptolide pretreatment.. Triptolide may function as an inhibitor of asthma airway remodeling by suppressing ASMCs proliferation via negative regulation of Smad signaling pathway.

Topics: Airway Remodeling; Animals; Anti-Inflammatory Agents, Non-Steroidal; Apoptosis; Asthma; Cell Proliferation; Cells, Cultured; Diterpenes; Epoxy Compounds; Immunosuppressive Agents; Male; Myocytes, Smooth Muscle; Phenanthrenes; Phosphorylation; Rats; Rats, Sprague-Dawley; S Phase Cell Cycle Checkpoints; Signal Transduction; Smad2 Protein; Smad3 Protein; Smad7 Protein; Transforming Growth Factor beta1

We have reported that triptolide inhibited pulmonary inflammation in patients with steroid-resistant asthma. In the present study, we investigated whether suppresses airway remodeling and goblet cell hyperplasia, studied the mechanism of triptolide on mucin5ac (Muc5ac) expression in a murine model of asthma.. BALB/c mice were sensitized to intraperitoneal ovalbumin (OVA) followed by repetitive ovalbumin challenge for 6 weeks. Treatments included triptolide (40 μg/kg) and dexamethasone (2mg/kg). The area of bronchial airway (WAt/Pbm), smooth muscle (WAm/Pbm) and mucus index were assessed 24h after the final OVA challenge. Levels of Muc5ac were assessed by ELISA, immunohistology and real-time PCR. Western blot was performed to analyze the phosphorylation of NF-κB p65.. Triptolide and dexamethasone significantly reduced allergen-induced increases in the thickness of bronchial airway, smooth muscle and goblet cell hyperplasia. Levels of lung Muc5ac and Muc5ac mRNA were significantly reduced in mice treated with triptolide and dexamethasone. Phosphorylation of NF-κB p65 was significantly reduced in mice treated with triptolide and dexamethasone.. Triptolide may inhibit airway goblet cell hyperplasia and Muc5ac expression in asthmatic mice via NF-κB. It may be a potential drug for the treatment of patients with severe asthma.

Topics: Airway Remodeling; Animals; Asthma; Blotting, Western; Bronchi; Bronchoalveolar Lavage Fluid; Disease Models, Animal; Diterpenes; Epoxy Compounds; Female; Goblet Cells; Hyperplasia; Hypertrophy; Mice, Inbred BALB C; Mucin 5AC; Mucus; NF-kappa B; Phenanthrenes; Phosphorylation; RNA, Messenger; Transcription Factor RelA

Airway remodelling contributes to increased morbidity and mortality in asthma. We have reported that triptolide, the major component responsible for the immunosuppressive and anti-inflammatory effects of Tripterygium wilfordii Hook F, inhibited pulmonary inflammation in patients with steroid-resistant asthma. In the present study, we investigated whether triptolide inhibits airway remodelling in a mouse asthma model and observed the effects of triptolide on the transforming growth factor-β₁ (TGF-β₁)/Smad pathway in ovalbumin (OVA)-sensitized mice. BALB/c mice were sensitized to intraperitoneal OVA followed by repetitive OVA challenge for 8 weeks. Treatments included triptolide (40 μg/kg) and dexamethasone (2 mg/kg). The area of bronchial airway (WAt/basement membrane perimeter) and smooth muscle (WAm/basement membrane perimeter), mucus index and collagen area were assessed 24 hr after the final OVA challenge. Levels of TGF-β(1) were assessed by immunohistology and ELISA, levels of TGF-β(1) mRNA were measured by RT-PCR, and levels of pSmad2/3 and Smad7 were assessed by Western blot. Triptolide and dexamethasone significantly reduced allergen-induced increases in the thickness of bronchial airway and smooth muscle, mucous gland hypertrophy, goblet cell hyperplasia and collagen deposition. Levels of lung TGF-β(1) , TGF-β(1) mRNA and pSmad2/3 were significantly reduced in mice treated with triptolide and dexamethasone, and this was associated with a significant increase in levels of Smad7. Triptolide may function as an inhibitor of asthma airway remodelling. It may be a potential drug for the treatment of patients with a severe asthma airway.

Topics: Airway Remodeling; Allergens; Animals; Asthma; Blotting, Western; Bronchoalveolar Lavage Fluid; Dexamethasone; Disease Models, Animal; Diterpenes; Enzyme-Linked Immunosorbent Assay; Epoxy Compounds; Female; Immunosuppressive Agents; Mice; Mice, Inbred BALB C; Ovalbumin; Phenanthrenes; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction; Smad Proteins; Transforming Growth Factor beta1

To explore the effect of triptolide on airway remodeling and the expression of nuclear factor-kappaB, Bcl-2 in asthmatic rats.. 40 rats were randomly divided into 5 groups (n = 8): (1) Control group; (2) Asthmatic 4 week group; (3) Asthmatic 6 week group; (4) Therapeutic 4 week group; (5) Therapeutic 6 week group. The airway resistance and eosinophilic inflammation of airway wall were observed. The airway wall thickness (WA/Pi), the bronchial smooth muscle thickness (smooth muscle area/Pi) and the number of bronchial smooth muscle nucleus (N/Pi) were measured by image analysis system. The expression of PCNA, nuclear factor-kappaB and Bcl-2 protein were determined by immunohistochemical staining and Western blot. The expression of Bcl-2 mRNA was determined by reverse transcription-polymerase chain reaction(RT-PCR).. (1) The expression of NF-kappaB protein in asthmatic 4 week group and asthmatic 6 week group was significantly higher than that in control group, respectively (P < 0.01). The above-mentioned parameters of therapeutic 6 week group were significantly lower than those of asthmatic 4 week group, asthmatic 6 week group and therapeutic 4 week group, respectively (P < 0.01, P < 0.01 P < 0.05). (2) The expression of Bcl-2 protein and mRNA of asthmatic 4 week group and asthmatic 6 week group were significantly higher than those in control group respectively (P < 0.01). The expression of Bcl-2 protein of therapeutic 6 week group was significantly lower than those of asthmatic 4 week group, asthmatic 6 week group and therapeutic 4 week group respectively (P < 0.05, P < 0.01, P < 0.01), but the expression of Bcl-2 mRNA was significantly higher than the above-mentioned groups respectively (P < 0.01), the expression of Bcl-2 protein and mRNA of therapeutic 6 week group were higher than control group respectively (P < 0.05, P < 0.01). (3) The expression of PCNA protein of asthmatic 4 week group and asthmatic 6 week group were significantly higher than those of control group respectively (P < 0.01). (4) The WA/ Pi, the smooth muscle area/Pi and the N/Pi of asthmatic 4 week group and asthmatic 6 week group were significantly higher than those of control group, respectively (P < 0.01). The above-mentioned parameters of therapeutic 6 week group were significantly lower than those of asthmatic 4 week group, asthmatic 6 week group and therapeutic 4 week group, respectively (P < 0.01). (5) The airway resistance of asthmatic 4 week group and asthmatic 6 week group were significantly higher than those of the control group, respectively (P < 0.01). The above-mentioned parameters of therapeutic 6 week group were significantly lower than those of asthmatic 4 week group, asthmatic 6 week group and therapeutic 4 week group, respectively (P < 0.01, P < 0.01, P < 0.05).. The proliferation of airway smooth muscle(ASM) is related with apoptosis of airway smooth muscle cells in asthma. NF-kappaB may be involved in the process. Triptolide may prevent apoptosis of ASMCs and decrease the proliferation of ASM by inhibiting the expression of NF-kappaB, Bcl-2.

Topics: Airway Remodeling; Animals; Apoptosis; Asthma; Bronchi; Diterpenes; Epoxy Compounds; Male; Myocytes, Smooth Muscle; NF-kappa B; Phenanthrenes; Proto-Oncogene Proteins c-bcl-2; Rats; Rats, Sprague-Dawley

The bone marrow eosinophilopoiesis makes a major contribution to the chronic airway inflammation in asthmatic animals and patients. Some anti-asthmatic medicines alleviated the asthmatic airway inflammation by inhibiting the bone marrow eosinophilopoiesis. Immunosuppressive agents have been commonly used in patients with glucocorticoid refractory asthma and have been proved to be effective. However, the research on the effect of the immunosuppressive agents on the bone marrow eosinophilopoiesis has seldom been reported. The purpose of the study was to explore the effect of mycophenolate mofetil (MMF) and triptolide (TP) on the bone marrow eosinophilopoiesis and to further investigate the mechanisms of the immunosuppressive agents involved in the anti-asthmatic effect. Balb/c mice were sensitized and challenged by OVA to establish the asthmatic model, and respectively administered orally with sterile saline, MMF, and TP once daily for 2 weeks. Airway inflammation, and inflammatory mediators IL-5 and eotaxin in the peripheral blood and bone marrow were measured by histology and ELISA. Immunocytochemistry combined with in situ hybridization technique and Western blot analysis was performed to estimate the amount of CD34+ IL-5R mRNA+ cells and IL-5R expression in the bone marrow. The count of new produced eosinophils in the bone marrow was detected by anti-BrdU immunocytochemistry. We found that MMF and TP attenuated OVA-induced eosinophil (EOS) recruitment in bronchoalveolar lavage fluid (BALF), inflammatory mediator expression of IL-5 and eotaxin in the peripheral blood, inflammatory cells expressing eotaxin in the lung tissues and the number of new produced EOS in the bone marrow. Also, MMF abated the migration of CD34+ cells from the bone marrow to the peripheral blood, which was associated with a decreased eotaxin expression in the bone marrow and a decreased CCR3 expression on bone marrow cells. While, MMF or TP failed to decrease the amount of CD34+ IL-5R mRNA+ cells (EOS progenitors), and IL-5R expression in the bone marrow of asthmatic model mice. These results demonstrated that MMF and TP reduce the eosinophilopoiesis of the bone marrow; this is associated with a decrease of IL-5 produced by T cells, which contribute to alleviate the allergic airway inflammation in asthma. In addition, MMF decreased the CD34+ cells migration from the bone marrow to the peripheral blood by the reduction of the level of eotaxin in the bone marrow and the expression of

Topics: Animals; Asthma; Bone Marrow; Diterpenes; Eosinophils; Epoxy Compounds; Hematopoiesis; Immunosuppressive Agents; Interleukin-5; Male; Mice; Mice, Inbred BALB C; Mycophenolic Acid; Phenanthrenes; Receptors, CCR3

To explore the effect of Triptolide on airway remodeling and the expression of Phosphoinositide 3-Kinases in asthmatic rats.. 40 rats were randomly divided into 5 groups (n = 8): (1) Control group; (2) Asthmatic 4 weeks group; (3) Asthmatic 6 weeks group; (4) Therapeutic 4 weeks group; (5) Therapeutic 6 weeks group. The airway resistance and eosinophilic inflammation of airway wall were observed. The airway wall thickness (WA/Pi), the bronchial smooth muscle thickness (smooth muscle area/Pi) and the number of bronchial smooth muscle nucleus (N/Pi) were measured by image analysis system. The expression of PI3K protein and mRNA were determined by immunohistochemical staining and reverse transcription-polymerase chain reaction (RT-PCR).. (1) The expression of PI3K p85alpha protein and mRNA in asthmatic 4 weeks group and asthmatic 6 weeks group were significantly higher than control group, respectively (P < 0.01). The above-mentioned parameters of therapeutic 6 weeks group were significantly lower than those of asthmatic 4 weeks group, asthmatic 6 weeks group and therapeutic 4 weeks group, respectively (P < 0.01, P < 0.01 P < 0.05). (2) The WA/Pi, the smooth muscle area/Pi and the N/Pi of asthmatic 4 weeks group and asthmatic 6 weeks group were significantly higher than control group, respectively (P < 0.01). The above-mentioned parameters of therapeutic 6 weeks group were significantly lower than those of asthmatic 4 weeks group, asthmatic 6 weeks group and therapeutic 4 weeks group, respectively (P < 0.01). (3) The airway resistance of asthmatic 4 weeks group and asthmatic 6 weeks group were significantly higher than the control group, respectively (P < 0.01). The above-mentioned parameters of therapeutic 6 weeks group were significantly lower than those of asthmatic 4 weeks group, asthmatic 6 weeks group and therapeutic 4 weeks group, respectively (P < 0.01, P < 0.01, P < 0.05).. The proliferation of airway smooth muscle is a remarkable character of airway remodeling in asthma. The PI3K signal pathway may be involved in the process. Triptolide may reduce AHR and decrease the proliferation of ASMCs by inhibiting the expression of PI3K. It may have potential therapeutic effects in the asthmatic airway remodeling.

Topics: Airway Remodeling; Animals; Asthma; Diterpenes; Epoxy Compounds; Male; Phenanthrenes; Phosphatidylinositol 3-Kinase; Rats; Rats, Sprague-Dawley; Signal Transduction

To investigate whether nuclear factor kappa B (NF-kappa B) participates in the regulatory function of lymphocyte proliferation and apoptosis in bronchial asthma and whether the regulatory effect of triptolide on lymphocyte proliferation and apoptosis is conducted through NF-kappa B.. Intervention with dexamethasone, triptolide and PDTC, a NF-kappa B inhibitor, were used to treat astmatic rats respectively. Pathological examination, airway response were determined, the NF-kappa B P65 expression in lung tissue and splenic lymphocytes by immunofluorescent assay were adopted, proliferative cell nuclear antigen (PCNA) in splenic lymphocytes was measured by immunohistochemistry, apoptosis of splenic lymphocytes were monitored by flow cytometry and NF-kappa B activity was investigated by electrophoresis mobility shift assay (EMSA).. The nuclear expression and DNA binding activity of lung tissue and splenic lymphocytes in asthmatic rats were all significantly higher than those in the control (all P < 0.05), so was the proliferation rate of splenic lymphocytes (P < 0.05), while the apoptosis rate was much lower than that of normal control (P < 0.05). Administration of PDTC could reduce the up-regulated expression and activity of NF-kappa B, the proliferation of splenic lymphocytes lowered, while the apoptosis increased. NF-kappa B activity showed an obviously positive correlation with proliferation of splenic lymphocytes (r = 0.89, P < 0.05) and a significantly negative correlation with apoptosis rate (r = -0.54, P < 0.05). After asthmatic rats had been treated with triptolide in vivo, the NF-kappa B nuclear expression and activity in airway and splenic lymphocytes, as well as the proliferation rate of splenic lymphocytes all lowered significantly (all P < 0.05), the apoptosis rate increased significantly (P < 0.05), at the same time, the inflammatory cell infiltration and high reactivity of airway were significantly alleviated (both P < 0.05). There were obviously positive correlation between the amount of airway eosinophils and reactivity with activity of NF-kappa B (r = 0.79 and r = 0.68, P < 0.05), which indicated that the effect of triptolide was not significantly different from that of dexamethasone (P > 0.05).. (1) NF-kappa B participates the formation of airway inflammation and hyper-reactivity in asthmatic rats by positive regulation on proliferation and negative regulation on apoptosis of lymphocytes. (2) Triptolide reduces airway inflammation by way of inhibiting NF-kappa B, and further inhibiting the proliferation of lymphocytes, so that to give full play of the role of anti-asthmatic airway inflammatory agents. Whether the molecular mechanism of triptolide in inhibiting NF-kappa B simulates that of glucocorticoid needs further studying.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Apoptosis; Asthma; Cell Division; Dexamethasone; Diterpenes; Epoxy Compounds; Lung; Lymphocytes; Male; NF-kappa B; Phenanthrenes; Random Allocation; Rats; Rats, Wistar; Transcription Factor RelA

To study the effect of triptolide on airway smooth muscle (ASM) proliferation and expressions of c-fos and c-jun in asthmatic rats.. 70 healthy male sprague-dawley rats were randomly divided into seven groups of 10 each. The asthmatic model was established by ovalbumin inhalation and injection. The mRNA expression of c-fos and c-jun were examined by RT-PCR and their protein expression by immunohistochemical method. The airway wall thickness, the ASM thickness, the number of ASM nucleus and pulmonary tissue changes were observed with microscope.. c-fos and c-jun mRNA and protein expressions of asthma groups A and five therapy groups (C, D, E, F and G) were significantly higher than those in the control group B (P < 0.01). The expressions were lower in group C, D, E, F and G than those in group A (P < 0.01). There was no significant difference in the expressions among group C, D, E, F and G (P > 0.05). Triptolide decreased ASM proliferation pathologically in asthmatic rats.. ASM proliferation is a feature of asthma. c-fos and c-jun may promote ASM proliferation in asthma. The remarkable inhibition of ASM proliferation by triptolide was probably due to its inhibitory effect on the expression of c-fos and c-jun.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Asthma; Bronchi; Cell Division; Diterpenes; Epoxy Compounds; Gene Expression Regulation; Male; Muscle, Smooth; Phenanthrenes; Proto-Oncogene Proteins c-fos; Proto-Oncogene Proteins c-jun; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger

Topics: Animals; Asthma; Caspases; Disease Models, Animal; Diterpenes; Epoxy Compounds; Guinea Pigs; Interleukin-1 Receptor-Associated Kinases; Lung; Male; Phenanthrenes; Proto-Oncogene Proteins c-bcl-2; Tripterygium

To observe the effect of Tripterygium wilfordii on Th1, Th2 cytokines in asthma patients for further study on the therapeutic mechanism.. Twelve patients of middle or severe asthma were treated by Tripterygium polyglucoside 40 mg or 60 mg daily for 4 weeks. Blood of patients was colleted before and after treatment for serum and peripherol blood mononuclear cells (PBMC) preparation. The prepared PBMCs were stimulted in vitro with Concanavalin A (ConA) for 6 hrs and followed by culturing with Triptolide for 24 hrs and then the supernatant was collected. The concentration of interleukin-2(IL-2), -4(IL-4), -5(IL-5) and interferon-gamma(IFN-gamma) in serum and in the supernatant were detected by enzyme-linked immunosorbent assay (ELISA).. Serum levels of IL-2, IL-4 and IL-5 of patients decreased significantly after treatment of Tripterygium polyglucoside (P < 0.01), but IFN-gamma level was under the detection sensitivity both before and after treatment. Triptolide could inhibit PBMC to secrete IL-2, IL-4 and IL-5 in vitro (P < 0.01), but IFN-gamma was also under the detection sensitivity.. The marked inhibition of Th2 cytokine expression by Tripterygium was the important mechanism of it in treating asthma. But the fact that Tripterygium also showed inhibition on Th1 cytokine indicated that the inhibition of Tripterygium on Th2 and Th1 cytokines was non-specific.

Topics: Adult; Asthma; Cells, Cultured; Diterpenes; Drugs, Chinese Herbal; Epoxy Compounds; Female; Glucosides; Humans; Interferon-gamma; Leukocytes, Mononuclear; Male; Middle Aged; Phenanthrenes; Phytotherapy; T-Lymphocytes, Helper-Inducer; Tripterygium

This article explores protein conjugation of 7-oxodehydroabietic acid, a resin acid found in both aerosol from soldering with rosin flux and in rosin solids. In a murine model, conjugation (haptenation) of resin acids to proteins is required to generate antibodies against rosin. Hydroperoxy resin acids are dermal sensitizers, with haptenation thought to occur via radical mechanisms. Dermal sensitization to 7-oxodehydroabietic acid has been observed, although no radical haptenation mechanism has been proposed to explain the sensitizing properties of this compound. Conjugation of L-lysine to 7-oxodehydroabietic acid was predicted, with a Schiff base (or imine) linkage formed between C-7 of the resin acid and a free amino group of lysine. Fast atom bombardment mass spectrometry provided evidence of the conjugate; a small peak was seen for the conjugate (M+H)+ ion in aqueous ethanol with 20 mM concentrations of the free resin and amino acids. A larger conjugate peak was observed with addition of tertiary amine as a mild basic catalyst, and the intensity of the conjugate peak exceeded that of the precursors upon replacement of the ethanol with benzene. Resin acids accumulate in the plasma membrane, a non-aqueous environment apparently conducive to conjugation of 7-oxodehydroabietic acid with lysine side chains of membrane proteins. The result would be dehydroabietic acid covalently bound to protein, which could lead to interaction with immune cells having resin acid specificity. The haptenation mechanism presented may be involved in allergic contact dermatitis and occupational asthma observed from exposure to resin acid solids and aerosols. As sampling and analytical methods have been previously demonstrated for 7-oxodehydroabietic acid, this compound may be a useful exposure marker with relevance to negative health effects such as occupational asthma.

Topics: Abietanes; Asthma; Dermatitis, Allergic Contact; Diterpenes; Haptens; Humans; Lysine; Occupational Diseases; Occupational Exposure; Phenanthrenes; Resins, Plant

Exposure to rosin during a variety of uses has been associated with dermal and pulmonary sensitization. Oxidized resin acids are present in many rosin products, and have been regarded as the main sensitizing rosin compounds in cases of dermal sensitization. This research describes oxidized resin acids identified in aerosol produced during soldering with rosin core solder. Oxidized resin acids found were 7-oxodehydroabietic acid, 15-hydroxydehydroabietic acid, and 7-hydroxydehydroabietic acid. The presence of oxidized compounds known to be dermal sensitizers in aerosol from rosin flux soldering supports the hypothesis that resin acid compounds are pulmonary sensitizers as previously proposed. Changes in the composition of resin acid aerosol derived from heated rosin core solder (compared with the parent material) are described.

Topics: Abietanes; Aerosols; Air Pollutants, Occupational; Asthma; Chromatography, Gas; Diterpenes; Environmental Monitoring; Humans; Mass Spectrometry; Oxidation-Reduction; Phenanthrenes; Resins, Plant

Various uses of rosin and exposure to its resin acid constituents have been associated with dermal and pulmonary sensitization. Methodology is presented to detect resin acids common to rosin (such as abietic and dehydroabietic acid) found in aerosol from heated rosin flux. Air filtration, solvent filter extraction, and gas chromatography/mass spectrometry were used to provide qualitative and quantitative information on the resin acid content of aerosol produced during soldering with rosin flux. Abietic acid and dehydroabietic acid were identified and quantified in aerosol derived from heated rosin flux, in samples collected in the field and in laboratory generated samples. Other resin acids (including several apparently oxidized resin acids) were detected, but not quantified. Laboratory mass balance experiments using soldering temperatures and liquid rosin flux showed that much of the nonvolatile material originally present in unheated flux may be captured on a sampling filter following heating and aerosolization. The data presented suggest that resin acids are a major component (with regard to mass) of the airborne contaminants produced during soldering with rosin flux. Abietic acid was shown to be unstable on sampling filters held for a period of weeks, while dehydroabietic acid and total solvent-soluble material were not found to degrade under the same conditions. Rosin aerosol produced in the laboratory using a soldering iron and liquid rosin flux produced particles shown to be of respirable size using scanning electron microscopy.

Topics: Abietanes; Aerosols; Air Pollutants, Occupational; Asthma; Diterpenes; Gas Chromatography-Mass Spectrometry; Humans; Microscopy, Electron, Scanning; Phenanthrenes; Resins, Plant

To explore the role of granulocyte-macrophage colony-stimulating factor (GM-CSF) in eosinophil inflammation of asthma airway.. Guinea pig models of asthma were established with aerosolized ovalbumin. A group of asthmatic guinea pigs were treated with injection of triptolide, density of eosinophil infiltration in airway tissues was observed under microscope and expression of GM-CSF mRNA in airway tissues was detected with dot hybridization by Dig-labeled cDNA probe.. Expression of GM-CSF mRNA in asthmatic animals were higher markedly than that in the triptolide-treated and the control groups. However, there was no statistically differences of density of eosinophils infiltration between the asthma and the triptolide-treated groups.. GM-CSF might participate in eosinophil inflammation in airway of asthmatic animals and triptolide might be of potential value in anti-inflammation for asthma.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Asthma; Diterpenes; Epoxy Compounds; Granulocyte-Macrophage Colony-Stimulating Factor; Guinea Pigs; Ovalbumin; Phenanthrenes; RNA, Messenger

Flux cored solder commonly used in the electronics industry is a metal alloy, based on tin and lead, and a flux consisting of colophony with a small concentration of an activator. Thirty-four electronics workers with occupational asthma and seventeen with respiratory symptoms, probably from other causes, have been investigated by occupational type bronchial provocation testing. All the sensitized workers had a significant fall in FEV1 after exposure to colophony fumes for 15 min or less. The non-sensitized workers had no significant reactivity to this test. There was little correlation between the reaction to colophony fumes and the non specific reactivity to histamine, suggesting that colophony fumes were causing specific sensitization. In sensitized workers Portuguese Y colophony was found to cause slightly larger reactions than similar exposures to American WW colophony. In the six workers tested reactions followed exposure to abietic acid alone, the principal resin acid in colophony. Methylation of the carboxyl group of colophony was associated with decreased reactivity. Workers with non-specific bronchial hyperreactivity also sometimes reacted after exposure to fumes from the flux activators alone, but even this reaction could show specificity for the specific activator to which the workers was exposed. Finally two non-colophony substitute materials were evaluated.

Topics: Abietanes; Allergens; Asthma; Bronchial Provocation Tests; Carboxylic Acids; Diterpenes; Electronics; Forced Expiratory Volume; Humans; Occupational Diseases; Phenanthrenes; Resins, Plant; Time Factors

Topics: Adenylyl Cyclases; Adult; Age Factors; Alkaloids; Asthma; Child; Enzyme Activation; Female; Humans; Indolizines; Leukocytes; Male; Middle Aged; Phenanthrenes; Reference Values