RESUMO
BACKGROUNDS: Treating asthmatic rheumatoid arthritis patients with abatacept has been shown to associate with better control of asthma symptoms. However, the mechanism behind that is not investigated. METHODS: Ovalbumin (OVA)- sensitized BALB/c female mice were treated intranasally (IN) or intraperitoneally (IP) with abatacept 4 hrs before the OVA challenge. The effects of abatacept IN or IP on the lungs and blood levels of Tregs and Bregs and their production of immunosuppressive cytokines, were determined using FACS analysis and ELISA assay. RESULTS: Treating OVA- sensitized asthmatic mice model with abatacept, IN or IP, reduced lung inflammation. IN treatment with abatacept increased the frequency of IL-35 and IL-10 producing Bregs in the lung tissues to a higher level compared to IP treatment. Moreover, the frequency of lungs LAG3+ Tregs was significantly increased following treatment. This was also associated with a reduction in lung tissue and serum IL-17 levels of treated mice. CONCLUSIONS: These results suggest that abatacept by enhancing IL-35+IL-10+ Bregs and LAG3+ Tregs might reverse IL-17 induced lung inflammation during asthma.
Assuntos
Asma , Interleucina-10 , Abatacepte/farmacologia , Abatacepte/uso terapêutico , Administração Intranasal , Animais , Asma/induzido quimicamente , Asma/tratamento farmacológico , Líquido da Lavagem Broncoalveolar , Modelos Animais de Doenças , Feminino , Interleucina-17 , Pulmão , Camundongos , Camundongos Endogâmicos BALB C , OvalbuminaRESUMO
Polycyclic aromatics hydrocarbons (PAHs) are ubiquitous and toxic pollutants that are dangerous to humans and living organism in aquatic environment. Normally, PAHs has lower molecular weight such as phenanthrene and naphthalene that are easy and efficient to degrade, but high-molecular-weight PAHs such as chrysene and pyrene are difficult to be biodegraded by common microorganism. This study investigated the isolation and characterization of a potential halophilic bacterium capable of utilizing two high-molecular-weight PAHs. At the end of the experiment (25-30 days of incubation), bacterial counts have reached a maximum level (over 40 × 1016 CFU/mL). The highest biodegradation rate of 77% of chrysene in 20 days and 92% of pyrene in 25 days was obtained at pH 7, temperature 25 °C, agitation of 150 rpm and Tween 80 surfactant showing to be the most impressive parameters for HMWPAHs biodegradation in this research. The metabolism of initial compounds revealed that Hortaea sp. B15 utilized pyrene to form phthalic acid while chrysene was metabolized to form 1-hydroxy-2-naphthoic acid. The result showed that Hortaea sp. B15 can be promoted for the study of in situ biodegradation of high molecular weight PAH.
Assuntos
Bactérias/crescimento & desenvolvimento , Crisenos/metabolismo , Hidrocarbonetos Policíclicos Aromáticos/metabolismo , Pirenos/metabolismoAssuntos
Asma/imunologia , Linfócitos B Reguladores/imunologia , Movimento Celular/imunologia , Quimiocina CXCL13/imunologia , Interleucina-17/imunologia , Pulmão/imunologia , Adulto , Asma/patologia , Linfócitos B Reguladores/patologia , Células Cultivadas , Feminino , Humanos , Pulmão/patologia , Masculino , Células Th17/imunologia , Células Th17/patologiaRESUMO
BACKGROUND: Although corticosteroid is a powerful anti-inflammatory drug that is used widely to control asthma, still severe asthmatics can develop steroid resistance. Airway fibroblasts are quite resistant to steroids during Idiopathic pulmonary fibrosis (IPF) and fibrosis in asthmatic lungs is not always controlled. Th-17 regulatory cytokine which are elevated in lung tissues of asthmatics were shown to enhance the survival of various types of cells. STAT factors are central to this anti-apoptotic function. However, it is not yet clear whether these cytokines contribute to steroid hypo-responsiveness in asthma. Therefore, in this study, we investigated the ability of Th-17 regulatory cytokines, specifically IL-21, IL22 and IL23, to protect structural airway cells against dexamethasone-induced apoptosis. METHODS: Primary human fibroblasts, ASM cells, and lung endothelial cells line were treated with IL-21, IL-22, and IL-23 cytokines before incubation with dexamethasone and the level of apoptosis was determined by measuring cellular Annexin-V using Flow cytometry. RESULTS: Our data indicated that treatment with Th-17 regulatory cytokines was effective in inhibiting induced apoptosis for both fibroblasts and endothelial cells but not ASM cells. STAT3 phosphorylation levels were also upregulated in fibroblasts and endothelial upon treatment with these cytokines. Interestingly, inhibiting STAT3 phosphorylation abrogated IL-21, IL-22, and IL-23 anti-apoptotic effect on fibroblasts and endothelial cells. CONCLUSIONS: This data suggest that Th-17 regulatory cytokines may play a critical role in regulating the survival of fibroblasts during asthma, IPF as well as other chronic lung inflammatory diseases leading to enhanced fibrosis. Accordingly, findings of this paper may pave the way for more extensive research on the role of these regulatory cytokines in fibrosis development in various chronic inflammatory diseases.
Assuntos
Apoptose/imunologia , Citocinas/imunologia , Dexametasona/administração & dosagem , Pulmão/citologia , Pulmão/imunologia , Células Th17/imunologia , Corticosteroides/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Apoptose/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Fatores Imunológicos/imunologia , Pulmão/efeitos dos fármacos , Células Th17/citologia , Células Th17/efeitos dos fármacosRESUMO
IL-17 is a pro-inflammatory mediator that is believed to play a critical role in regulating tissue inflammation during asthma, COPD, as well as other inflammatory disorders. The level of expression of IL-17 has been shown to be upregulated in lung bronchial tissue of asthmatic patients. Several reports have provided further evidence that this cytokine could play a key role in enhancing the migration of inflammatory as well as structural cells of the bronchial lung tissue during asthma and COPD. B cell infiltration to sites of inflammation during inflammatory disorders such as bowel disease, asthma and COPD has been reported. Accordingly, in this study we hypothesized that IL-17 may exert a chemotactic effect on primary B cells during asthma. We observed that B cells from asthmatic patients expressed significantly higher levels of IL-17RA and IL-17RC, compared to those of healthy subjects. Using an in-vitro migration assay, B cells were shown to migrate towards both IL-17A and IL-17F. Interestingly, blocking IL-17A and IL-17F signaling using either anti-IL-17R antibodies or MAP kinase inhibitors prevented in vitro migration of B cell towards IL-17. These observations indicate a direct chemotactic effect of IL-17 cytokines on primary peripheral blood B cells with higher effect being on asthmatic B cells. These findings revealed a key role for IL-17 in enhancing the migration of B cells to the lung tissue during asthma or COPD.