title: TRPV1 inhibition attenuates IL-13 mediated asthma features in mice by reducing airway epithelial injury.
abstract: Even though neurogenic axis is well known in asthma pathogenesis much attention had not been given on this aspect. Recent studies have reported the importance of TRP channels, calcium-permeable ion channels and key molecules in neurogenic axis, in asthma therapeutics. The role of TRPV1 channels has been underestimated in chronic respiratory diseases as TRPV1 knockout mice of C57BL/6 strains did not attenuate the features of these diseases. However, this could be due to strain differences in the distribution of airway capsaicin receptors. Here, we show that TRPV1 inhibition attenuates IL-13 induced asthma features by reducing airway epithelial injury in BALB/c mice. We found that IL-13 increased not only the lung TRPV1 levels but also TRPV1 expression in bronchial epithelia in BALB/c rather than in C57BL/6 mice. TRPV1 knockdown attenuated airway hyperresponsiveness, airway inflammation, goblet cell metaplasia and subepithelial fibrosis induced by IL-13 in BALB/c mice. Further, TRPV1 siRNA treatment reduced not only the cytosolic calpain and mitochondrial calpain 10 activities in the lung but also bronchial epithelial apoptosis indicating that TRPV1 siRNA might have corrected the intracellular and intramitochondrial calcium overload and its consequent apoptosis. Knockdown of IL-13 in allergen induced asthmatic mice reduced TRPV1, cytochrome c, and activities of calpain and caspase 3 in lung cytosol. Thus, these findings suggest that induction of TRPV1 with IL-13 in bronchial epithelia could lead to epithelial injury in in vivo condition. Since TRPV1 expression is correlated with human asthma severity, TRPV1 inhibition could be beneficial in attenuating airway epithelial injury and asthma features.
authors: CSIR-Institute of Genomics and Integrative Biology, Mall Road, Delhi, India.
authors: Rakhshinda
authors: R
authors: Rehman
authors: Younus Ahmad
authors: YA
authors: Bhat
authors: Lipsa
authors: L
authors: Panda
authors: Ulaganathan
authors: U
authors: Mabalirajan
mesh_terms: D000818:Animals; D001249:Asthma / Q000235:genetics / Q000276:immunology*; D016535:Bronchial Hyperreactivity / Q000235:genetics; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000235:genetics; D055785:Gene Knockdown Techniques; D020397:Goblet Cells / Q000473:pathology; D006801:Humans; D018793:Interleukin-13 / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D034741:RNA, Small Interfering / Q000235:genetics; D020545:Respiratory Mucosa / Q000276:immunology*; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism*
chemical_list: D016207:Cytokines; D018793:Interleukin-13; D034741:RNA, Small Interfering; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse