Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học 'Respiratory Research cung cấp cho các bạn kiến thức về ngành y đề tài:Pro-inflammatory mechanisms of muscarinic receptor stimulation in airway smooth muscle. | Oenema et al. Respiratory Research 2010 11 130 http content 11 1 130 RESPIRATORY RESEARCH RESEARCH Open Access Pro-inflammatory mechanisms of muscarinic receptor stimulation in airway smooth muscle 1 1 1 3 Tjitske A Oenema Saeed Kolahian Janke E Nanninga Danielle Rieks Pieter S Hiemstra Suzanne Zuyderduyn3 Andrew J Halayko4 Herman Meurs1 Reinoud Gosens1 Abstract Background Acetylcholine the primary parasympathetic neurotransmitter in the airways plays an important role in bronchoconstriction and mucus production. Recently it has been shown that acetylcholine by acting on muscarinic receptors is also involved in airway inflammation and remodelling. The mechanism s by which muscarinic receptors regulate inflammatory responses are however still unknown. Methods The present study was aimed at characterizing the effect of muscarinic receptor stimulation on cytokine secretion by human airway smooth muscle cells hASMc and to dissect the intracellular signalling mechanisms involved. hASMc expressing functional muscarinic M2 and M3 receptors were stimulated with the muscarinic receptor agonist methacholine alone and in combination with cigarette smoke extract CSE TNF-a PDGF-AB or IL-1p. Results Muscarinic receptor stimulation induced modest IL-8 secretion by itself yet augmented IL-8 secretion in combination with CSE TNF-a or PDGF-AB but not with IL-1Ị3. Pretreatment with GF109203X a protein kinase C PKC inhibitor completely normalized the effect of methacholine on CSE-induced IL-8 secretion whereas PMA a PKC activator mimicked the effects of methacholine inducing IL-8 secretion and augmenting the effects of CSE. Similar inhibition was observed using inhibitors of kB-kinase-2 SC514 and MEK1 2 U0126 both downstream effectors of PKC. Accordingly western blot analysis revealed that methacholine augmented the degradation of IftBa and the phosphorylation of ERK1 2 in combination with CSE but not with IL-1b in hASMc. Conclusions We conclude that .
