Abstract
BackgroundMany studies have found that smoking reduces lung function, but the relationship between cigarette smoke and allergic asthma has not been clearly elucidated, particularly the role of mast cells. This study aimed to investigate the effects of smoke exposure on allergic asthma and its association with mast cells.MethodsBALB/c mice were sensitized and challenged by OVA to induce asthma, and bone marrow-derived mast cells (BMMCs) were stimulated with antigen/antibody reaction. Mice or BMMCs were exposed to cigarette smoke or CSE solution for 1 mo or 6 h, respectively. The recruitment of inflammatory cells into BAL fluid or lung tissues was determined by Diff-Quik or H&E staining, collagen deposition by Sircol assay, penh values by a whole-body plethysmography, co-localization of tryptase and Smad3 by immunohistochemistry, IgE and TGF-β level by ELISA, expressions of Smads proteins, activities of signaling molecules, or TGF-β mRNA by immunoblotting and RT-PCR.ResultsCigarette smoke enhanced OVA-specific IgE levels, penh values, recruitment of inflammatory cells including mast cells, expressions of smad family, TGF-β mRNA and proteins, and cytokines, phosphorylations of Smad2 and 3, and MAP kinases, co-localization of tryptase and Smad3, and collagen deposition more than those of BAL cells and lung tissues of OVA-induced allergic mice. CSE solution pretreatment enhanced expressions of TGF-β, Smad3, activities of MAP kinases, NF-κB/AP-1 or PAI-1 more than those of activated-BMMCs.ConclusionsThe data suggest that smoke exposure enhances antigen-induced mast cell activation via TGF-β/Smad signaling pathways in mouse allergic asthma, and that it exacerbates airway inflammation and remodeling.
Highlights
Many studies have found that smoking reduces lung function, but the relationship between cigarette smoke and allergic asthma has not been clearly elucidated, the role of mast cells
In view of the fact that Smad3 siRNA transfection did not induce the activities of NF-B or PAI-1 in Smad3 downstream signal cascades in bone marrow-derived mast cells (BMMCs), we suggest that cigarette smoke may induce collagen deposition by mast cell activation through TGF-b/Smad signaling pathways
The present study suggests that cigarette smoke exposure in part up-regulates antigen-induced mast cell activation associated with allergic asthma through TGF-b/ pSmadL/NF-B and AP-1 signaling pathway, and upregulated mast cells induce the production of cytokines and collagen deposition, and that it may exacerbate airway inflammation and tissue remodeling in mouse allergic asthma
Summary
Many studies have found that smoking reduces lung function, but the relationship between cigarette smoke and allergic asthma has not been clearly elucidated, the role of mast cells. Cigarette smoke contains many toxic substances and a strong pro-inflammatory stimulus [1,2,3] It is widely recognized as a significant risk factor for a number of diseases including emphysema, chronic obstructive pulmonary disease, cardiovascular disease, lung cancer and allergic diseases [1]. It was recently shown that TGF-b/Smad signaling proteins were expressed in the majority of cells infiltrating into the airway in mouse models [19,20,21,22] and human asthma [19,23]
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