Ding, Shengang published the artcileInflammatory cytokines tumour necrosis factor-α and interleukin-8 enhance airway smooth muscle contraction by increasing L-type Ca2+ channel expression, Quality Control of 21829-25-4, the main research area is TNFalpha IL8 airway smooth muscle contraction LVDCC asthma; IL-8; L-type Ca2+ channel; TNF-α; airway smooth muscle; asthma; inflammation.
Inflammation elevates intracellular calcium concentrations ([Ca2+]i) in airway smooth muscle (ASM). The L-type Ca2+ channel (L-VDCC) plays an important role in regulating Ca2+ influx in ASM. However, the role of L-VDCC in the inflammatory cytokine-induced pathol. of ASM remains unclear. In the present study, we used calcium imaging and isometric tension measurements to assess the role of L-VDCC in agonist-induced [Ca2+]i rise and the associated contractions in mouse ASM, and we used immunoblotting to identify L-VDCC protein expression levels in mouse ASM after exposure to tumor necrosis factor alpha (TNF-a) or interleukin-8 (IL-8). Our results showed that high-K+- or carbachol-induced contractions of mouse ASM were significantly greater after pretreatment with TNF-α or IL-8 for 24 h. Both verapamil and nifedipine, L-VDCC inhibitors, abolished this increased contraction induced by TNF-α or IL-8 pretreatment. Moreover, TNF-α treatment enhanced carbachol-induced Ca2+ influx in ASM cells, and this effect was abrogated by verapamil. Addnl., immunoblotting results showed that preincubation of mouse ASM with TNF-α or IL-8 also enhanced L-VDCC protein expression. On the basis of these findings, we concluded that proinflammatory cytokines, such as TNF-α and IL-8, increase the expression level of L-VDCC, which in turn contributes to augmented agonist-induced ASM contractions. This effect of inflammation on L-VDCC expression in ASM may be associated with airway hyper-responsiveness and involved in the development of asthma.
Clinical and Experimental Pharmacology and Physiology published new progress about Asthma. 21829-25-4 belongs to class pyridine-derivatives, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Quality Control of 21829-25-4.