Abstract
BackgroundWhile the presence of the chitinase-like molecule YKL40 has been reported in COPD and asthma, its relevance to inflammatory processes elicited by cigarette smoke and common environmental allergens, such as house dust mite (HDM), is not well understood. The objective of the current study was to assess expression and function of BRP-39, the murine equivalent of YKL40 in a murine model of cigarette smoke-induced inflammation and contrast expression and function to a model of HDM-induced allergic airway inflammation.MethodsCD1, C57BL/6, and BALB/c mice were room air- or cigarette smoke-exposed for 4 days in a whole-body exposure system. In separate experiments, BALB/c mice were challenged with HDM extract once a day for 10 days. BRP-39 was assessed by ELISA and immunohistochemistry. IL-13, IL-1R1, IL-18, and BRP-39 knock out (KO) mice were utilized to assess the mechanism and relevance of BRP-39 in cigarette smoke- and HDM-induced airway inflammation.ResultsCigarette smoke exposure elicited a robust induction of BRP-39 but not the catalytically active chitinase, AMCase, in lung epithelial cells and alveolar macrophages of all mouse strains tested. Both BRP-39 and AMCase were increased in lung tissue after HDM exposure. Examining smoke-exposed IL-1R1, IL-18, and IL-13 deficient mice, BRP-39 induction was found to be IL-1 and not IL-18 or IL-13 dependent, while induction of BRP-39 by HDM was independent of IL-1 and IL-13. Despite the importance of BRP-39 in cellular inflammation in HDM-induced airway inflammation, BRP-39 was found to be redundant for cigarette smoke-induced airway inflammation and the adjuvant properties of cigarette smoke.ConclusionsThese data highlight the contrast between the importance of BRP-39 in HDM- and cigarette smoke-induced inflammation. While functionally important in HDM-induced inflammation, BRP-39 is a biomarker of cigarette smoke induced inflammation which is the byproduct of an IL-1 inflammatory pathway.
Highlights
While the presence of the chitinase-like molecule YKL40 has been reported in Chronic obstructive pulmonary disease (COPD) and asthma, its relevance to inflammatory processes elicited by cigarette smoke and common environmental allergens, such as house dust mite (HDM), is not well understood
Cigarette smoke-induced inflammation and expression of chitinases and chitinase-like molecules To investigate the impact of cigarette smoke exposure on chitinase expression, BALB/c, C57BL/6, and CD1 mice were exposed to cigarette smoke twice daily for a 4 day period
Since chitinase expression can be induced by cigarette smoke in humans [17], we sought to measure breast regression protein (BRP)-39 and acidic mammalian chitinase (AMCase) expression in lung homogenates of room air- and cigarette smoke-exposed BALB/c, C57BL/6, and CD1 mice
Summary
While the presence of the chitinase-like molecule YKL40 has been reported in COPD and asthma, its relevance to inflammatory processes elicited by cigarette smoke and common environmental allergens, such as house dust mite (HDM), is not well understood. It is well understood that family-18 glycosyl hydrolases such as the chitinase-like molecule YKL-40 and the murine homologue breast regression protein (BRP)-39 are upregulated in a variety of inflammatory conditions [12,13,14]. Two members of this family of enzymatically active and inactive chitinases, acidic mammalian chitinase (AMCase) and BRP-39 have been shown to be crucial in murine models of allergic inflammation. Murine models may be utilized to investigate the importance of BRP-39 in cigarette smokeinduced inflammatory processes relative to the already established importance of BRP-39 in models of allergic airway disease
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