The

mechanism by which GM-CSF induces collagen synthesis is not completely clear, but it could be due to induction of TGF-β, a known regulator of connective tissue synthesis. GM-CSF was shown to induce TGF-β mRNA expression in vascular smooth muscle and in leiomyoma cells (Brown et al., 2001). These data corroborate our findings, reinforcing the observed increase in the lung remodeling in the OVA + CS group. VEGF is involved in angiogenesis and remodeling and is an autocrine survival factor for epithelial Target Selective Inhibitor Library manufacturer cells (St-Laurent et al., 2009). St-Laurent et al. (2009) studied the bronchial epithelial cells from challenged OVA-sensitized rats and showed an increase in VEGF after 5 days of cigarette smoke extract exposure, and the cigarette smoke-exposed groups also had an increase in VEGF levels. Our data compares favorably with reports from cell-based studies (Brown et al., 2001) that showed an increase in VEGF levels in groups exposed to cigarette smoke and reinforce the increase in pulmonary remodeling in this experimental model. Cigarette smoke is known to have immunomodulatory properties, but the extent to which smoking cigarettes can alter airway immunity in asthma is not well established (Trimble et al., 2009). Our results showed a significant difference in IFN-γ levels in the OVA + CS group compared with all of the other groups. CS stimuli

selleck products alone were insufficient to produce an increase in lung IFN-γ levels, suggesting an additional effect of CS on allergic lung inflammation. Although this most likely reflects the toxic effects of cigarette smoke, it

is noteworthy that IFN-γ did not abolish, but decreased significantly, the eosinophilic inflammation as expected (Cho et al., 2005, Hofstra et al., 1998 and Sopori and Kozak, 1998). In addition, elevated levels of IFN-γ were found in the sputum of patients with asthma, also suggesting that the pathology of asthma could be partially IFN-γ driven (Cho et al., 2005 and Sopori ever and Kozak, 1998). Many chemical components of cigarette smoke can affect immune function (Sopori and Kozak, 1998 and Nouri-Shirazi et al., 2007). One of the most potent and reactive cigarette smoke components is acrolein. Acrolein can influence IL-10, a cytokine with regulatory and anti-inflammatory characteristics capable of inhibiting antigen presentation in macrophages/monocytes (Hristova et al., 2012). This inhibition results in the abrogation of proliferative responses and a decrease in T cell cytokine production (Li et al., 1997, Li et al., 1999, Li and Holian, 1998 and Seymour et al., 1997). This mechanism may be involved in our experimental model because animals exposed to cigarette smoke showed high levels of cytokines in the lung tissue and elevated expression of IL-10 in the bronchial epithelial cells (Kasahara et al., 2008).