Abstract
Asthma is an allergic lung disease and, when associated to cigarette smoke exposition, some patients show controversial signs about lung function and other inflammatory mediators. Epidemiologic and experimental studies have shown both increasing and decreasing inflammation in lungs of subjects with asthma and exposed to cigarette smoke. Therefore, in this study, we analyzed how cigarette smoke affects pro-inflammatory and anti-inflammatory mediators in a murine model of allergic pulmonary inflammation. We sensitized Balb/c mice to ovalbumin (OVA) with two intraperitoneal injections. After sensitization, the animals were exposed to cigarette smoke twice a day, 30 min per exposition, for 12 consecutive days. In order to drive the cell to the lungs, four aerosol challenges were performed every 48 h with the same allergen of sensitization. OVA sensitization and challenge developed pulmonary Th2 characteristic response with increased airway responsiveness, remodeling, increased levels of IgE, interleukin (IL)-4, and IL-13. Cigarette smoke, unexpectedly, reduced the levels of IL-4 and IL-13 and simultaneously decreased anti-inflammatory cytokines as IL-10 and transforming growth factor (TGF)-β in sensitized and challenged animals. OVA combined with cigarette smoke exposition decreased the number of eosinophils in bronchoalveolar lavage and increased the number of neutrophils in lung. The combination of cigarette smoke and lung allergy increased recruitment of lymphoid dendritic cells (DCs) into lymph nodes, which may be the leading cause to an increase in number and activation of CD8+ T cells in lungs. In addition, lung allergy and cigarette smoke exposure decreased an important regulatory subtype of DC such as plasmacytoid DC as well as its activation by expression of CD86, PDL2, and ICOSL, and it was sufficient to decrease T regs influx and anti-inflammatory cytokines release such as IL-10 and TGF-β but not enough to diminish the structural changes. In conclusion, we observed, in this model, that OVA sensitization and challenge combined with cigarette smoke exposure leads to mischaracterization of the Th2 response of asthma by decreasing the number of eosinophils, IL-4, and IL-13 and increasing number of neutrophils, which is related to the increased number of CD8ɑ+ DCs and CD8+ T cells as well as reduction of the regulatory cells and its released cytokines.
Highlights
Asthma is among the most prominent and severe types of allergic diseases, affecting 300 million people worldwide [1]
We still observed that the combination of cigarette smoke exposure in this model of asthma caused higher deposition of collagen fibers over the airway when compared to CS alone and OVA group and promoted hyperplasia/hypertrophy of bronchial epithelial cells (Figures 1H–J)
Cigarette smoke exposure associated with OVA sensitization caused bronchial epithelial cell remodeling, increased the number of neutrophils and activated type 2 macrophages, increased the number and activation of CD4+ and CD8+ T cells and decreased Plasmacytoid DCs (pDCs) and its activation by reducing expression of CD86, ICOSL, and PDL2
Summary
Asthma is among the most prominent and severe types of allergic diseases, affecting 300 million people worldwide [1]. The pulmonary response to allergens is initiated by the activated epithelium-releasing TSLP, interleukin (IL)-25, and IL-33 that activate innate immune cells such as ILC2s. The environment created by inflammatory cytokines and inflammatory cells activate the adaptive immune system characteristically denominated as a persistent Th2 inflammation. As a counter regulatory response, regulatory T cells (Tregs) are recruited to the site of inflammation and released cytokine such as IL-10. This cytokine is often but not always capable of attenuating Th2 response in some models of lung allergy and; it plays a protective role in allergic asthma [6]
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