Effects Of Staphylococcus Aureus On The Activation Of JNK And Secretion Of Th1/Th2Cytokines In Murine Macrophage

Background The most common inflammatory diseases of the airwaysare asthma and chronic obstructive pulmonary disease (COPD), and theincidence of both is increasing throughout the world, imposing enormousburdens onhealth care. It has shown that bacterial infections not only led to thediseases acute exacerbate, but also involved in development and incidence of chronicinflammatory diseases of the airway. Especially in recent years found thatstaphylococcus aureus (S.aureus) is closely related to the onset of asthma and COPD.Macrophages in the innate immune system as the first line of defense against pathogens,through its specific Pattern recognition receptors (PRR) to participate in the immuneresponse. After the PAMP interaction with TLR, through their Toll/IL–1R domainrecruit MyD88protein and then activated the NF-κB and MAPK signal pathway, avariety of cytokines and chemokines, adhesion molecules and other pro-inflammatorymolecules, which in turn helps to remove leukocyte recruitment and bacteria. Studyfound that TLR2can recognize Gram-positive bacteria such as S.aureus andGram-positive bacterial LTA and peptidoglycan (PGN)). After S.aureus to stimulateTLR2can activate split the original mitogen-activated protein kinase (MAPK) familymembers--extracellular signal-regulated kinase（ERK）,p38and c-Jun amino terminalkinase (JNK). After JNK/MAPK activation can induce the expression of multiple genesinvolved in regulating the inflammatory response.Objective To investigate the effects on c-Jun amino-terminal kinase (JNK) expression and Th1/Th2cytokines secretion from mouse macrophage cell line RAW264.7stimulated by S.aureus.Methods RAW264.7cells were cultured in vitro, then were stimulated by S.aureusat a multiplicity of infection (MOI) of10(S. aureus: cells=10:1) for0.5,1.0,1.5and2.0h respectively. The protein expression of P-JNK was analyzed by Western blot, thelevel of Interleukin-5(IL-5) and interferon-γ (IFN-γ) in the supernatants of each groupwere analyzed by ELISA.Results After stimulating by S.aureus, the level of JNK phosphorylation wassignificantly increased and was maximized at0.5h (P <0.01);the level of IFN-γ weresignificantly increased at0.5,1.0h (P <0.01), but back to normal level at1.5and2.0h(P>0.05); IL-5began to increase at1h and1.5h (P <0.05), and was significantly higherat2.0h (P <0.01); Additionally, the ratio of IL-5/IFN-γ was significantly increased at1.0,1.5and2h compared to0.5h.(P <0.01).Conclusion S.aureus stimulation activated JNK signaling and regulated the balanceof Th1/Th2cytokines in murine macrophages.