ovalbumin and phthalic-acid

Endocrine disrupting chemicals have been known to contribute to the aggravation of inflammatory diseases including asthma. We aimed to investigate the effects of mono-n-butyl phthalate (MnBP) which is one of the representing phthalates, and its antagonist in an eosinophilic asthma mouse model. BALB/c mice were sensitized by intraperitoneal injection of ovalbumin (OVA) with alum and followed by three nebulized OVA challenges. MnBP was administered through drinking water administration throughout the study period, and its antagonist, apigenin, was orally treated for 14 days before OVA challenges. Mice were assessed for airway hyperresponsiveness (AHR), differential cell count and type 2 cytokines in bronchoalveolar lavage fluid were measured in vivo. The expression of the aryl hydrocarbon receptor was markedly increased when MnBP was administered. MnBP treatment increased AHR, airway inflammatory cells (including eosinophils), and type 2 cytokines following OVA challenge compared to vehicle-treated mice. However, apigenin treatment reduced all asthma features, such as AHR, airway inflammation, type 2 cytokines, and the expression of the aryl hydrocarbon receptor in MnBP-augmented eosinophilic asthma. Our study suggests that MnBP exposure may increase the risk of eosinophilic inflammation, and apigenin treatment may be a potential therapy for asthma exacerbated by endocrine-disrupting chemicals.

Topics: Animals; Apigenin; Asthma; Bronchoalveolar Lavage Fluid; Cytokines; Disease Models, Animal; Inflammation; Lung; Mice; Mice, Inbred BALB C; Ovalbumin; Receptors, Aryl Hydrocarbon

Increasing attention has been paid to the potential impact of microplastics (MPs) pollution on human health. MPs and phthalates coexist in the environment, however, the effects of exposure to MPs alone or to a combination of di-(2-ethylhexyl) phthalate (DEHP) and MPs on allergic asthma are unclear. This study investigates the effects of exposure to polystyrene microplastics (PS-MPs) or co-exposure with DEHP, on allergic asthma, and the underlying molecular mechanisms. We established an allergic asthma model using ovalbumin, and mice were exposed to PS-MPs (5 mg/kg bw/day) alone, or combined with DEHP (0.5, 5 mg/kg bw/day), for 28 days. The results showed that in the presence of ovalbumin (OVA) sensitization, exposure to PS-MPs alone slightly affected airway inflammation, and airway hyperresponsiveness, while co-exposure to PS-MPs and DEHP caused more significant damage. Co-exposure also induced more oxidative stress and Th2 immune responses, and activation of the TRPA1 and p38 MAPK pathways. The aggravation of asthmatic symptoms induced by co-exposure to PS-MPs and DEHP were inhibited by blocking TRPA1 ion channel or p38 MAPK pathway. The results demonstrated that co-exposure to PS-MPs and DEHP exacerbates allergic asthma, by exacerbating oxidative stress and inflammatory responses, and activating the TRPA1-p38 MAPK pathway.

Topics: Animals; Asthma; Diethylhexyl Phthalate; Mice; Microplastics; Ovalbumin; p38 Mitogen-Activated Protein Kinases; Plastics; Polystyrenes; TRPA1 Cation Channel

To investigate the effects of exposure to diethyl phthalate(DEHP) during pregnancy and lactation in respiratory allergy of offspring Wistar rats.. To establish the maternal DEHP exposure model: 36 healthy 2-month-old female Wistar rats were divided into three different dose groups. From GD0, each group of pregnant mice were given different concentrations of DEHP(0, 30, 300 mg/(kg·d)) until to the newborn weaning(PND21). After birth, one of offspring was selected from each cage in different dose groups. At PND21 and PND28 the offspring were sensitized by intraperitoneal injection(i. p. ) OVA and continuous nasal sensitization at PND32, PND33, PND34. Bronchoalveolar lavage fluid(BALF) and lung tissue were collected at PND35 with non-sensitized groups. ELISA detected the secretion of Th2 cytokine interleukin(IL)-4, IL-5 and IL-13 in BALF, and the pathological changes of allergic inflammation in lung tissues were observed by HE and PAS staining. Expression of epithelium-derived factor IL-33 detected by immunohistochemistry.. In BALF, compared with the control group, the total number of inflammatory cells and eosinophils in the DEHP0+OVA group increased to(131. 500±25. 548)×10~4, (32. 000±10. 079)×10~4(P<0. 05); The total number of inflammatory cells and eosinophils in the DEHP30+OVA group increased to(156. 167±17. 994)×10~4, (16. 331±6. 667)×10~4(P<0. 05); and the total number of inflammatory cells and eosinophils in the DEHP300+OVA group increased to(172. 167±19. 994)×10~4, (55. 000±17. 018)×10~4(P<0. 05). After adding different doses of DEHP and OVA, compared with the control group, The expression levels of IL-4, IL-5, IL-13 in DEHP0+OVA group increased to(38. 401±6. 594) pg/mL(P>0. 05), (30. 026±2. 756) pg/mL(P<0. 05), (13. 806±4. 355) pg/mL(P<0. 05); The expression levels of IL-4, IL-5 and IL-13 in DEHP30+OVA group increased to(57. 733±7. 293) pg/mL(P<0. 05) and(31. 544±1. 043) pg/mL(P>0. 05), (18. 068±1. 497) pg/mL(P<0. 05); The expression levels of IL-4, IL-5 and IL-13 in DEHP300+OVA group increased to(54. 943±6. 049) pg/mL(P>0. 05) and(32. 377±3. 739)pg/mL(P>0. 05), (20. 168±0. 939) pg/mL(P<0. 05), respectively. The tissue section of all the DEHP+saline groups could be observed that no obvious allergic inflammatory reaction, meanwhile all the DEHP+OVA groups had a relatively obvious allergic reaction and were severe with the increase of DEHP dose. Immunohistochemistry showed no significant increase in the expression of IL-33 in the DEHP+saline groups, while the expression of IL-33 in the DEHP+OVA groups increased with a certain dose response.. Exposure to DEHP during pregnancy and lactation will aggravate the sensitization reaction of offspring, the possible mechanism that DEHP increase the Th2 type of immune response may be the overexpression of IL-33 in the epithelial cells.

Topics: Animals; Asthma; Bronchoalveolar Lavage Fluid; Disease Models, Animal; Female; Humans; Hypersensitivity; Interleukin-33; Lactation; Mice; Mice, Inbred BALB C; Ovalbumin; Phthalic Acids; Pregnancy; Rats; Rats, Wistar

Previously, we demonstrated that maternal exposure to phthalates enhances atopic dermatitis in male mouse offspring. However, whether phthalate exposure affects neuroimmune biomarkers in allergic mice has not yet been studied. Di-(2-ethylhexyl) phthalate (DEHP) and di-isononyl phthalate (DINP) are environmental chemicals that are commonly used as plasticizers. This study was designed to investigate the expression levels of neuroimmune biomarkers in the hypothalamus of a murine model of allergic asthma after phthalate exposure throughout juvenility until adulthood. Six-week-old C3H/HeJ Jcl male mice were treated with DEHP or DINP (0, 0.02, 0.4 or 8 nmol per body per week) and ovalbumin (OVA; 1 µg per body per 2 weeks) for 7 weeks intratracheally. On the day after the completion of the phthalate and OVA treatment, the hypothalamus from each mouse was collected, and the mRNA expression levels of neuroimmune biomarkers were examined using a real-time RT-PCR analysis. The mRNA expression levels of the proinflammatory cytokines interleukin (IL)-1β and tumor necrosis factor (TNF)-α, the chemokine CCL3, the transcription factor nuclear factor (NF)-κB, the oxidative stress marker heme-oxygenase (HO)1, a nerve growth factor, and the microglia marker Iba1 were remarkably up-regulated in the hypothalami of mice treated with 8 nmol of DEHP in the presence of the allergen. However, no significant changes were observed, except for reductions in the TNF-α and CCL2 mRNA levels, in mice exposed to DINP combined with the allergen. This study is the first report to show that high-dose DEHP exposure throughout juvenility until adulthood may induce neuroinflammation by modulating neuroimmune biomarkers in the hypothalami of allergic mice.

Topics: Allergens; Animals; Asthma; Biomarkers; Chemokine CCL3; Diethylhexyl Phthalate; Dose-Response Relationship, Drug; Heme Oxygenase-1; Hypothalamus; Interleukin-1beta; Male; Membrane Proteins; Mice; Mice, Inbred C3H; Neurogenic Inflammation; NF-kappa B; Ovalbumin; Oxidative Stress; Phthalic Acids; Plasticizers; RNA, Messenger; Tumor Necrosis Factor-alpha; Up-Regulation

Terpenoids are ubiquitous natural compounds that have been shown to improve vaccine efficacy as adjuvants. To gain an understanding of the structural features important for adjuvanticity, we studied compounds derived from a diterpene phytol and assessed their efficacy. In a previous report, we showed that phytol and one of its derivatives, PHIS-01 (a phytol-derived immunostimulant, phytanol), are excellent adjuvants. To determine the effects of varying the polar terminus of PHIS-01, we designed amine and mannose-terminated phytol derivatives (PHIS-02 and PHIS-03, respectively). We studied their relative efficacy as emulsions with soluble proteins, ovalbumin, and a hapten-protein conjugate phthalate-KLH. Immunological parameters evaluated consisted of specific antibody responses in terms of titers, specificities and isotype profiles, T cell involvement and cytokine production. Our results indicate that these new isoprenoids were safe adjuvants with the ability to significantly augment immunogen-specific IgG1 and IgG2a antibody responses. Moreover, there was no adverse phthalate cross-reactive anti-DNA response. Interestingly, PHIS-01 and PHIS-03 influenced differentially T-helper polarization. We also observed that these compounds modulated the immune response through apoptotic/necrotic effects on target tumor cells using murine lymphomas. Finally, unlike squalene and several other terpenoids reported to date, these phytol derivatives did not appear arthritogenic in murine models.

Topics: Adjuvants, Immunologic; Animals; Apoptosis; Cytokines; Diterpenes; Emulsions; Female; Haptens; Hemocyanins; Immunity, Humoral; Immunoglobulin Class Switching; Immunoglobulin G; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Necrosis; Ovalbumin; Phthalic Acids; Phytol; T-Lymphocytes, Helper-Inducer; Vaccines

In a recent study, di-(2-ethylhexyl) phthalate (DEHP) and its metabolite, mono-2-ethylhexyl phthalate, were shown to possess adjuvant effect [Toxicology 169 (2001) 37; Toxicology Letters 125 (2001) 11]. The present study investigates the adjuvant effect of another important commercial phthalate plasticizer, benzyl butyl phthalate (BBP) as well as its degradation products, phthalic acid and benzyl alcohol (BA) in a murine model. The model antigen, ovalbumin (OA), was injected either alone (OA control group), together with one of the test substances (test group) or together with aluminium hydroxide, which served as the positive adjuvant control. The mice were boosted either once or twice with OA before blood was collected and assayed for the content of OA-specific IgE, IgG1 and IgG2a antibodies by ELISA methods. Adjuvant effect was defined as a statistically significant increased antibody level in the test groups compared with the OA control group. Conversely, if the antibody production in a test group was significantly lower than the OA control group, it was deemed to be immunosuppression. This study demonstrated that BBP, in contrast to DEHP, did not possess adjuvant effect. Furthermore, immunosuppression was apparent in the case of BA. The study also demonstrated that if the injections give rise to formation of wounds, it may cause false positive results.

Topics: Adjuvants, Immunologic; Animals; Benzyl Alcohol; Dose-Response Relationship, Immunologic; Enzyme-Linked Immunosorbent Assay; Female; Immunization, Secondary; Immunoglobulin E; Immunoglobulin G; Immunosuppressive Agents; Injections, Subcutaneous; Mice; Mice, Inbred BALB C; Ovalbumin; Phthalic Acids; Random Allocation

The prevalence of allergic airway diseases is rapidly increasing in Western Europe and North America. This increase in disease prevalence may be associated with environmental pollutants. The present study investigated the adjuvant and immuno-suppressive effect of a series of monophthalates which are considered to be important metabolites of commonly used phthalate plasticizers. The effects were studied in a screening model. Ovalbumin (OA), used as the model antigen, was injected subcutaneously in the neck region of BALB/cJ mice with or without one of the test substances, mono-n-butyl phthalate (MnBP), monobenzyl phthalate (MBnP), mono-n-octyl phthalate (MnOP), mono-2-ethylhexyl phthalate (MEHP), mono-iso-nonyl phthalate (MiNP) or mono-iso-decyl phthalate (MiDP). The levels of OA-specific IgE, IgG1 and IgG2a in sera were measured by ELISA. Immuno-suppressive effect, defined as a statistically significant reduction in IgE or IgG1 antibody production, was observed with MEHP (1000 microg/ml, IgE and IgG1), MnOP (1000 microg/ml, IgE and IgG1), MiNP (1000 microg/ml, IgE and 10 microg/ml, IgG1) and MiDP (100 microg/ml, IgE and IgG1). Adjuvant effect, defined as a statistically significant increase in IgE or IgG1 antibody level, occurred with MEHP (10 microg/ml, IgE), MnOP (100 microg/ml, and 10 microg/ml, IgG1) and MiNP (100 microg/ml, IgE). No statistically significant immune modulating effect was seen with MBnP and MnBP.

Topics: Adjuvants, Immunologic; Animals; Environmental Pollutants; Female; Immunoglobulins; Immunosuppressive Agents; Mice; Mice, Inbred BALB C; No-Observed-Adverse-Effect Level; Ovalbumin; Phthalic Acids; Random Allocation; Statistics, Nonparametric; Structure-Activity Relationship