interleukin-8 and sodium-bisulfide

Hydrogen sulfide (H. In the experiment, the T1DM animal model was established, the IL-1β, IL-8 were determined by western blotting and ELISA, the expressions of the Bax and Bcl-2 of endothelial cells and the CXCR2, CSE, phosphor-IκBα and NF-kB of neutrophils were measured by western blotting. Additionally, the concentration of serum dsDNA was tested by PicoGreen commercial Kits, changes in the H

Topics: Animals; Diabetes Mellitus, Type 1; Endothelial Cells; Hydrogen Sulfide; Interleukin-8; Neutrophils; NF-kappa B; NF-KappaB Inhibitor alpha; Rats; Reactive Oxygen Species; Receptors, Interleukin-8B; Sulfides

Topics: Cell Survival; Cells, Cultured; Diabetic Angiopathies; Glucose; Human Umbilical Vein Endothelial Cells; Humans; Inflammation; Interleukin-1beta; Interleukin-6; Interleukin-8; MAP Kinase Signaling System; Membrane Potential, Mitochondrial; Necroptosis; p38 Mitogen-Activated Protein Kinases; Protective Agents; Reactive Oxygen Species; Receptor-Interacting Protein Serine-Threonine Kinases; Signal Transduction; Sulfides; Tumor Necrosis Factor-alpha

Bamboo salt (BS) is a Korean traditional type of salt and has been reported to have therapeutic effects on allergic inflammation. Thymic stromal lymphopoietin (TSLP) aggravates inflammation in the pathogenesis of allergic reactions, such as allergic rhinitis (AR). To confirm an active compound of BS, we investigated the effect of sulfur, a compound of BS, on the levels of TSLP in a human mast cell line, HMC-1 cells and a mouse model of AR using hydrogen sulfide (H2S) donor, sodium hydrosulfide (NaSH). We treated NaSH or BS in HMC-1 cells and activated the HMC-1 cells with phorbol myristate acetate and calcium ionophore A23187 (PMACI). ELISA for the production measurement of TSLP, PCR for the mRNA expression measurement of TSLP, and western blot analysis for the expression measurement of upstream mediators were performed. Mice were treated with NaSH and sensitized with ovalbumin (OVA). The levels of TSLP were measured in serum and nasal mucosa tissue in an OVA-induced AR mouse model. NaSH or BS diminished the production and mRNA expression of TSLP as well as interleukin (IL)-6 and tumor necrosis factor (TNF)-α in the PMACI-activated HMC-1 cells. NaSH or BS diminished the level of intracellular calcium in the PMACI-activated HMC-1 cells. NaSH or BS reduced the expression and activity of caspase-1 in the PMACI-activated HMC-1 cells. And NaSH or BS inhibited the expression of receptor interacting protein-2 and the phosphorylation of extracellular signal-regulated kinase in the PMACI-activated HMC-1 cells. The translocation of NF-κB into the nucleus as well as the phosphorylation and degradation of IκBα in the cytoplasm were diminished by NaSH or BS in the PMACI-activated HMC-1 cells. Furthermore, NaSH inhibited the production of TSLP, IL-6, and IL-8 in TNF-α-activated HMC-1 cells. Finally, the administration of NaSH showed a decrease in number of rubs on mice with OVA-induced AR. And the levels of immunoglobulin E and TSLP in the serum and the level of TSLP in the nasal mucosa tissue of the OVA-induced AR mice were reduced by NaSH. In conclusion, these findings show that H2S, as an active compound of BS is a potential agent to cure allergic inflammation.

Topics: Active Transport, Cell Nucleus; Animals; Calcimycin; Calcium; Caspase 1; Cell Line; Cytokines; Extracellular Signal-Regulated MAP Kinases; Female; Humans; Hydrogen Sulfide; I-kappa B Proteins; Immunoglobulin E; Interleukin-6; Interleukin-8; Mast Cells; Medicine, Korean Traditional; Mice; Mice, Inbred BALB C; NF-kappa B; NF-KappaB Inhibitor alpha; Ovalbumin; Phosphorylation; Real-Time Polymerase Chain Reaction; Receptor-Interacting Protein Serine-Threonine Kinase 2; Rhinitis, Allergic; RNA, Messenger; Sulfides; Tetradecanoylphorbol Acetate; Thymic Stromal Lymphopoietin; Tumor Necrosis Factor-alpha

Balneotherapy employing sulphurous thermal water is still applied to patients suffering from diseases of musculoskeletal system like osteoarthritis (OA) but evidence for its clinical effectiveness is scarce. Since the gasotransmitter hydrogen sulphide (H2 S) seems to affect cells involved in degenerative joint diseases, it was the objective of this study to investigate the effects of exogenous H2 S on fibroblast-like synoviocytes (FLS), which are key players in OA pathogenesis being capable of producing pro-inflammatory cytokines and matrix degrading enzymes. To address this issue primary FLS derived from OA patients were stimulated with IL-1β and treated with the H2 S donor NaHS. Cellular responses were analysed by ELISA, quantitative real-time PCR, phospho-MAPkinase array and Western blotting. Treatment-induced effects on cellular structure and synovial architecture were investigated in three-dimensional extracellular matrix micromasses. NaHS treatment reduced both spontaneous and IL-1β-induced secretion of IL-6, IL-8 and RANTES in different experimental settings. In addition, NaHS treatment reduced the expression of matrix metallo-proteinases MMP-2 and MMP-14. IL-1β induced the phosphorylation of several MAPkinases. NaHS treatment partially reduced IL-1β-induced activation of several MAPK whereas it increased phosphorylation of pro-survival factor Akt1/2. When cultured in spherical micromasses, FLS intentionally established a synovial lining layer-like structure; stimulation with IL-1β altered the architecture of micromasses leading to hyperplasia of the lining layer which was completely inhibited by concomitant exposure to NaHS. These data suggest that H2 S partially antagonizes IL-1β stimulation via selective manipulation of the MAPkinase and the PI3K/Akt pathways which may encourage development of novel drugs for treatment of OA.

Topics: Cell Survival; Cells, Cultured; Chemokine CCL5; Enzyme Activation; Extracellular Space; Fibroblasts; Humans; Hydrogen Sulfide; Interleukin-1beta; Interleukin-6; Interleukin-8; Matrix Metalloproteinase 14; Matrix Metalloproteinase 2; Mitogen-Activated Protein Kinases; Osteoarthritis; Phosphorylation; Proto-Oncogene Proteins c-akt; Sulfides; Synovial Membrane

Oxidative stress and inflammation play crucial role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Most patients with COPD show a poor response to corticosteroids. Hydrogen sulfide (H2S ) has been implicated in the pathogenesis of COPD, but its expression and effects in lung tissue from COPD patients are not clear. In peripheral lung tissue samples from 24 patients, we found that compared with nonsmokers, the protein level of cystathionine-γ-lyase (CSE) was decreased in smokers and COPD patients. CSE mRNA increased but cystathionine-β-synthase (CBS) mRNA decreased in COPD patients. H2S donors increased glutathione and superoxide dismutase in CS exposed U937 cells and inhibited CS-induced TNF-α and IL-8 secretion. Dexamethasone alone had no effect on lipopolysaccharide (LPS) induced TNF-α release by alveolar macrophages from CS exposed rats, however the combination of dexamethasone and H2S donor significantly inhibited TNF-α release. Thus, H2S metabolism is altered in lung tissue of smokers and COPD patients. Supplementation of H2S protects against CS-induced oxidative stress and inflammation in macrophages and H2S on steroid sensitivity deserves further investigation.

Topics: Adrenal Cortex Hormones; Animals; Anti-Inflammatory Agents; Cell Line, Tumor; Cystathionine beta-Synthase; Cystathionine gamma-Lyase; Dexamethasone; Gene Expression Regulation; Glutathione; Humans; Hydrogen Sulfide; Inflammation; Interleukin-8; Lipopolysaccharides; Lung; Macrophages; Oxidative Stress; Pulmonary Disease, Chronic Obstructive; Rats; Rats, Sprague-Dawley; RNA, Messenger; Signal Transduction; Smoking; Sulfides; Superoxide Dismutase; Tumor Necrosis Factor-alpha

Hydrogen sulfide (H2S) is a naturally occurring gaseous transmitter, which is important in normal physiology and disease. In the present study, the involvement of H2S in the regulation of the immune response induced by burn injury was investigated in mice. Adult male C57BL/6 mice were subjected to burn injuries and treated with vehicle (0.9% sodium chloride, NaCl; 100 ml/kg body weight; subcutaneously, s.c.) or the H2S donor (sodium hydrosulfide, NaHS; 2 mg/kg body weight; s.c.). Compared with the controls, mice which received burn injuries exhibited a significant decrease in plasma H2S levels. Moreover, the levels of tumor necrosis factor (TNF)‑α, interleukin (IL)‑6 and IL‑8 significantly increased, while IL‑10 levels were decreased, compared with that of the controls in the plasma of mice subjected to burn injuries. Myeloperoxidase (MPO) activity in the liver tissue of injured mice was also markedly higher compared with that of the control group. However, the administration of NaHS significantly decreased the levels of TNF‑α, IL‑6 and IL‑8 but increased the levels of IL‑10 in the plasma of mice subjected to burn injuries. In addition, the MPO activity was decreased by NaHS. These results suggested that H2S regulates the inflammatory response induced by burn injury by modulating the levels of TNF‑α, IL‑6, IL‑8 and IL‑10. Thus, it was proposed that the administration of the H2S donor, NaHS, may be a useful therapy against the exaggerated immune response that is associated with burn injury.

Topics: Animals; Anti-Inflammatory Agents; Burns; Hydrogen Sulfide; Inflammation Mediators; Interleukin-10; Interleukin-6; Interleukin-8; Liver; Male; Mice; Mice, Inbred C57BL; Peroxidase; Sulfides; Tumor Necrosis Factor-alpha

To investigate the effect of hydrogen sulfide (H2S) on the expression of CSE, NF-κB, and IL-8 mRNA in GES-1 cells with Helicobacter pylori (H. pylori) infection and to explore its mechanism on gastric mucosa inflammation caused by H. pylori.. GES-1 cells were cultured for 24 h and divided into a control group (neither H. pylori nor NaHS), an H. pylori group, a NaHS group (which was further divided into 4 groups at 50, 100, 200, or 400 μmol/L NaHS), and H. pylori + NaHS group (which was further divided into 4 groups at 50, 100, 200, or 400 μmol/L NaHS). Each group was then cultured for 3, 6, or 12 h. The expression of CSE, NF-κB, and IL-8 mRNA was measured by RT-PCR, and their correlation was analyzed.. The expression of CSE, NF-κB, and IL-8 mRNA in GES-1 cells in the H. pylori group was higher than that in the control group. The expression of CSE in the 200 μmol/L NaHS group and 400 μmol/L NaHS group was lower than that of the control group (P<0.05), whereas the expression of NF-κB and IL-8 in all NaHS groups had no statistical differences compared with the control group (P>0.05). The expression of CSE, NF-κB, and IL-8 mRNA in all groups of NaHS, H. pylori + 200 μmol/L NaHS group, and H. pylori + 400 μmol/L NaHS group was lower than that in the H. pylori group (P<0.05). There was positive correlation among the expressions of CSE, NF-κB, and IL-8 mRNA in the H. pylori group, the H. pylori + 200 μmol/L NaHS group, and the H. pylori + 400 μmol/L NaHS group (P<0.05).. H. pylori can induce NF-κB and IL-8 mRNA expression and upregulate CSE mRNA expression. At 200 and 400 μmol/L, NaHS can suppress H. pylori-induced NF-κB and IL-8 mRNA expression and ameliorate the morphology of H. pylori-induced GES-1 injury, which may protect gastric epithelial cells by H. pylori infection.

Topics: Cell Line; Cystathionine gamma-Lyase; Epithelial Cells; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Hydrogen Sulfide; Interleukin-8; NF-kappa B; RNA, Messenger; Sulfides

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disorder, primarily affecting the articular structures and synovial membranes of multiple joints. Beside pharmacologically based treatments, sulphur bath therapy has long been used as a therapy for patients suffering from different rheumatic disorders. But scientific reports about the beneficial effects of H(2)S as well as about the underlying molecular mechanisms are controversial and rare.. Fibroblast-like synoviocytes (FLS) derived from RA and OA-patients were treated with the H(2)S-donor sodium hydrogen sulphide (NaHS). IL-6 release was quantified by enzyme-linked immunosorbent assay (ELISA). Gene expression of IL-6, IL-8 and COX-2 as well as of the matrix metalloproteinases (MMPs) MMP-2, MMP-3 and MMP-14 was monitored by quantitative real-time PCR (qRT-PCR). Modulation of the mitogen-activated protein kinases (MAPKs) p38 and ERK1/2 was analysed by Western blotting.. High concentrations of H(2)S (above 0.5mM) elevated the expression of pro-inflammatory genes in RA- and OA-FLS. This was accompanied by activation of p38 and ERK1/2 MAPK. H(2)S-induced expression of IL-6, IL-8 and COX-2 was completely blocked by specific inhibitors of p38 and ERK1/2 MAPK and NF-κB.. H(2)S is a potent gaseous molecule that can upregulate the expression of a series of pro-inflammatory genes in RA and OA-FLS. Therefore, caution is advised in patients with active RA when taking sulphur bath therapy.

Topics: Arthritis, Rheumatoid; Balneology; Cells, Cultured; Cyclooxygenase 2; Fibroblasts; Gene Expression Regulation; Humans; Hydrogen Sulfide; Inflammation Mediators; Interleukin-6; Interleukin-8; MAP Kinase Signaling System; Matrix Metalloproteinases; Mineral Waters; Osteoarthritis; Sulfides; Synovial Membrane

Hydrogen sulfide (H₂S), recently considered the third endogenous gaseous transmitter, may have an important role in systemic inflammation. We investigated whether endogenous H₂S may be a crucial mediator in airway responsiveness and airway inflammation in a rat model of chronic exposure to cigarette smoke (CS). Rats randomly divided into control and CS-exposed groups were treated with or without sodium hydrosulfide (NaHS, donor of H₂S) or propargylglycine (PPG, inhibitor of cystathionine-γ-lyase [CSE], an H₂S-synthesizing enzyme) for 4-month exposure. Serum H₂S level and CSE protein expression in lung tissue were higher, by 2.04- and 2.33-fold, respectively, in CS-exposed rats than in controls (P<0.05). Exogenous administration of NaHS to CS-exposed rats alleviated airway reactivity induced by acetylcholine (Ach) or potassium chloride (KCl) by 17.4% and 13.8%, respectively, decreased lung pathology score by 32.7%, inhibited IL-8 and TNF- α concentrations in lung tissue by 34.2% and 31.4%, respectively, as compared with CS-exposed rats (all P<0.05). However, blocking endogenous CSE with PPG in CS-exposed rats increased airway reactivity induced by Ach or KCl, by 24.1% and 24.5%, respectively, and aggravated lung pathology score, by 44.8%, as compared with CS-exposed rats (all P<0.01). Incubation in vitro with NaHS, 1-3 mmol/L, relaxed rat tracheal smooth muscle precontracted by Ach or KCl. However, the NaHS-induced relaxation was not blocked by glibenclamide (10⁻⁴ mol/L), L-NAME (10⁻⁴ mol/L), or ODQ (1 μmol/L) or denudation of epithelium. Endogenous H₂S may have a protective role of anti-inflammation and bronchodilation in chronic CS-induced pulmonary injury.

Topics: Acetylcholine; Alkynes; Animals; Cystathionine gamma-Lyase; Dose-Response Relationship, Drug; Enzyme-Linked Immunosorbent Assay; Glycine; Hydrogen Sulfide; In Vitro Techniques; Inflammation; Interleukin-8; Lung; Male; Muscle Contraction; Muscle, Smooth; Nicotiana; Random Allocation; Rats; Rats, Sprague-Dawley; Respiratory Hypersensitivity; Smoke; Sulfides; Trachea; Tumor Necrosis Factor-alpha; Vasodilator Agents

Hydrogen sulfide (H(2)S) is synthesized intracellularly by the enzymes cystathionine-γ-lyase and cystathionine-β-synthase (CBS), and is proposed to be a gasotransmitter with effects in modulating inflammation and cellular proliferation. We determined a role of H(2)S in airway smooth muscle (ASM) function. ASM were removed from resection or transplant donor lungs and were placed in culture. Proliferation of ASM was induced by FCS and the proinflammatory cytokine, IL-1β. Proliferation of ASM and IL-8 release were measured by bromodeoxyuridine incorporation and ELISA, respectively. Exposure of ASM to H(2)S "donors" inhibited this proliferation and IL-8 release. Methemoglobin, a scavenger of endogenous H(2)S, increased DNA synthesis induced by FCS and IL-1β. In addition, methemoglobin increased IL-8 release induced by FCS, but not by IL-1β, indicating a role for endogenous H(2)S in these systems. Inhibition of CBS, but not cystathionine-γ-lyase, reversed the inhibitory effect of H(2)S on proliferation and IL-8 release, indicating that this is dependent on CBS. CBS mRNA and protein expression were inhibited by H(2)S donors, and were increased by methemoglobin, indicating that CBS is the main enzyme responsible for endogenous H(2)S production. Finally, we found that exogenous H(2)S inhibited the phosphorylation of extracellular signal-regulated kinase-1/2 and p38, which could represent a mechanism by which H(2)S inhibited cellular proliferation and IL-8 release. In summary, H(2)S production provides a novel mechanism for regulation of ASM proliferation and IL-8 release. Therefore, regulation of H(2)S may represent a novel approach to controlling ASM proliferation and cytokine release that is found in patients with asthma.

Topics: Bronchi; Cell Proliferation; Cells, Cultured; Cystathionine beta-Synthase; Cystathionine gamma-Lyase; Dose-Response Relationship, Drug; Enzyme-Linked Immunosorbent Assay; Humans; Hydrogen Sulfide; Interleukin-1beta; Interleukin-8; Methemoglobin; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Morpholines; Myocytes, Smooth Muscle; Organothiophosphorus Compounds; p38 Mitogen-Activated Protein Kinases; Protein Kinase Inhibitors; Serum; Sulfides

To investigate the effects of hydrogen sulfide (H2S) on vascular inflammation in pulmonary hypertension induced by high pulmonary blood flow.. Forty-four male SD rats were randomly divided into 8 groups: 4-week control group (n = 7), 4-week shunt group (n = 7), 4-week shunt + propargylglycine (PPG, an endogenous H2S release inhibitor) intraperitoneal injection group (n = 8), 11-week control group (n = 7), 11-week shunt group (n = 7), and 11-week shunt + sodium hydrosulfide (NaHS, a H2S donor) intraperitoneal injection group (n = 8). Right ventricular catheterization was used to measure the mean pulmonary arterial pressure (mPAP). Immunohistochemistry was used to detect the expression of inflammatory related factor intercellular adhesion molecule-1 (ICAM-1), and the key molecules of nuclear factor-kappaB (NF-kappaB) signal transduction pathway, including NF-kappaB p65 and inhibitor of NF-kappaB (IkappaBalpha), in the pulmonary artery, and ELISA was used to detect the concentrations of the inflammatory related factors, including ICAM-1, interleukin-8 (IL-8), and monocyte chemoattractant protein-1 (MCP-1) in blood plasma and lung tissues so as to reflect the corresponding inflammatory responsiveness.. The plasma and lung tissue ICAM-1, IL-8 and MCP-1 contents of the 4-week shunt group were all significantly higher than those of the 4-week control group (P < 0.05 or P < 0.01). The mPAP of the 4 week shunt + PPG group was (20.3 +/- 1.7) mm Hg, significantly higher than that of the 4-week shunt group [(16.2 +/- 1.5) mm Hg, P < 0.01]. The expression levels of ICAM-1 and NF-kappaB p65 in the small and median pulmonary artery endothelin cells of the 4-week shunt + PPG group were both significantly stronger than those of the 4-week shunt group (P < 0.05 or P < 0.01), whereas the expression of IkappaBalpha was weaker than that of the 4-week shunt group (P < 0.05). The plasma IL-8 content of the 4-week shunt + PPG group was (148 +/- 29) micromol/L, significantly higher than that of the 4 week-shunt group [(118 +/- 23) micromol/L, P < 0.05], and the lung tissue ICAM-1 and MCP-1 levels of the 4-week shunt + PPG group were (27.3 +/- 5.0) micromol/g and (12.9 +/- 1.1) micromol/g respectively, both significantly higher than those of the 4-week shunt group [(21.9 +/- 2.1) and (10.2 +/- 1.4) micromol/g respectively, both P < 0.05]. The mPAP and expression levels of ICAM-1 and NF-kappaB p65 of the large, median, and small pulmonary artery endothelia cells of the 11-week shunt group were all higher than those of the 11-week control group (P < 0.05 or P < 0.01), whereas the expression levels of IkappaBalpha were all less obvious (P < 0.05 or P < 0.01). The plasma and lung tissue ICAM-1, IL-8, and MCP-1 levels of the 11-week shunt group were all significantly higher than those of the 11-week control group (all P < 0.01). The mPAP of the 11 week shunt + NaHS group was (23.2 +/- 3.0) mm Hg, significantly lower than that of the 11-week shunt group [(27.5 +/- 1.9) mm Hg, P < 0.05]. The ICAM-1 and NF-kappaB p65 expression levels of large, median, and small pulmonary artery endothelia cells of the 11-week shunt + NaHS group were all significantly weaker than those of the 11-week shunt group (P < 0.05 or P < 0.01), whereas the protein expression levels of IkappaBalpha in small and median pulmonary artery endothelia cells of the 11-week shunt + NaHS group were significantly higher than those of the 11-week shunt group (both P < 0.05). The plasma and lung tissue ICAM-1 contents of the 11-week shunt + NaHS group were (124 +/- 11) micromol/L and (19.9 +/- 2.5) micromol/g, both significantly lower than those of the 11-week shunt group [(154 +/- 20) micromol/L and (23.9 +/- 3.6) micro. H2S attenuates the development of pulmonary hypertension induced by high pulmonary blood flow through ameliorating pulmonary vascular inflammation. The inhibitory effect of H2S on the pulmonary vascular inflammation involves elevating IkappaBalpha expression, down-regulating NF-kappaB p65 expression and then inhibiting the expression of inflammatory related factors.

Topics: Animals; Chemokine CCL2; Hydrogen Sulfide; Hypertension, Pulmonary; Immunohistochemistry; Injections, Intraperitoneal; Intercellular Adhesion Molecule-1; Interleukin-8; Lung; Male; Pulmonary Artery; Pulmonary Circulation; Random Allocation; Rats; Rats, Sprague-Dawley; Sulfides; Transcription Factor RelA; Vasculitis