C-Jun N-terminal Kinase Mediated By Toll Like Receptor 2 In The Pathogenesis Of Murine Asthma

Background Bronchial asthma(asthma) is the chronic airway allergic disease involved many genes, a kind of immune disease in unbalance.Its morbidity and mortality rates tend to rise in recent years, causing serious medical burden.Its pathogenesis is not yet clear.At present, toll-like receptor 2(TLR2), an important member of toll-like receptors(TLRs) family, has been reported not only to participate in the inherent immune responses, but also mediate the adaptive immune response.It plays an significant role in the development of asthma, but the specific function and mechanism hasn’t yet known to us, even there exsits controversy. The artificial ligand of TLR2, Pam3 Cys, has been showed to activate antigen presenting cells, such as DC. Then DC mediated initial Th0 cell differentiation into Th2 cell and suppression Th1 cell,thus promoting experimental asthma, while there had opposite conclusions.TLR2 gene mutation is an important factor in the susceptibility of asthma.After TLR2 combined with the ligand,its intracellular homologous Toll/IL-1receptor(TIR) region could recruit and activate several critical signaling molecules, such as c-Jun amino terminal kinase/Mitogen Activated Protein Kinase(JNK/MAPK),transcription factor- ? B.Then the intranuclear transcription factor was expressed,thus promoting the release of intracellular inflammatory factors. JNK,as the important member of MAPK,was reported to play a pivotal role in multiple aspects of asthma,such as chronic airway inflammation, airway smooth muscle thickening and airway hyperresponsiveness.Early in the staphylococcus aureus stimulating alveolar cell line RAW264.7 experiment, TLR2 was found to activate and mediate JNK signaling pathway.While TLR2 mediated JNK signaling molecules involved in allegic inflammation pathogenesis hasn’t yet to be reported.Objective To explore the mechanism of c-Jun N-terminal kinase mediated by Toll like receptor 2 in murine asthma.Methods 14 healthy SPF grade C57 wild-type mice and 14 TLR2 knockout(TLR2-/-)mice were randomly divided into four groups of C57 control group, C57 asthma group,TLR2-/- control group, TLR2-/- asthma group(n = 7). HE-staining was applied to detecte pathological changes in each group. We utilized intraperitoneal injection combined with inhalation of ovalbumin(OVA) to sensitize and challenge the mice, thus establishing the experimental models of asthma.Meanwhile, the control group received normal saline instead of OVA.The protein expression of TLR2 was detected by immunohistochemistry(ABC method) in C57 control group and C57 asthma group,as well as JNK and phosphorylation c-Jun(P-JNK) between each group.Results In C57 asthma group and TLR2-/- asthma group,HE-staining showed more obvious inflammatory cell infiltration around bronchi and airway smooth muscle hyperplasia than the compared groups. The relative protein expression were measured by mean absorbance(m A). Immunohistochemistry indicated that mean absorbance values of TLR2 were significantly higher in C57 asthma group than those of C57 control group(P<0.01). There was no obvious difference of JNK protein expression between each group(P>0.05). The immunoexpression of P-JNK in C57 asthma group were notablely higher than those of C57 control group, TLR2-/- asthma group, TLR2-/-control group(F=43.261,P<0.01).Conclusion TLR2-mediated JNK signaling molecules may be involved in the process of murine allegic inflammation.