The Effect Of Valnemulin On The Expression Of TLR4and CD14in Acute Lung Injury Mice Induced By Lipopolysaccharide

Acute lung injury (ALI) is a common clinical critically disease, which is cause by a variety ofrisk factors internal or external lung excluding cardiogenic factors, leading the damage ofpulmonary capillary endothelial cells and alveolar epithelial cells, diffuse interstitial lung oralveolar edema and pulmonary acute inflammation. The major mechanism of ALI isinflammatory reaction which is caused by endotoxin (LPS). LBP can promote the bindingbetween LPS and membrane CD14of mononuclear/macrophage cells, to form the complex ofLPS-LBP-CDl4and to activate mononuclear/macrophage cells by MyD88、IRAK、TRAF6, andTIRAP、MAL, which activate NF-kappa B and MAPKs signal transduction pathway and releasea variety of proinflammatory cytokines and inflammatory mediators. The proinflammatorycytokines and inflammatory mediators cause the aggregation of neutrophilic leukocytes, andultimately leading to ALI.Valnemulin is a new semi-synthetic analog of the two terpenes class of antibiotics that isdesigned for treatment of animal infections. The previous reports of LPS induced ALI focus ondownstream cytokines in LPS signal transduction pathway, these results showed that valnemulinhad a protective effect on LPS-induced inflammatory lung injury in mice through to inhibit theproduction of TNF-α, IL-6and IL-1β in mice monocytes and macrophages. The purpose of thisstudy was to evaluate anti-inflammatory effect of valnemulin on RAW264.7cells and ALIinduced by LPS in mice. In our study, real-time PCR and western blot were used to detect theeffect of valnemulin on LPS signal transduction pathway in RAW264.7cells, the results showedthat the expression of TLR4and CD14were much higher in the LPS group and significantlydrcreased by valnemulin in a dose-dependent manner.To Provide objective evaluation index onclinical therapeutic of valnemulin,we used a mouse model of LPS-induced inflammatory lunginjury.In vivo study, valnemulin markedly suppressed the production of TLR4and CD14in adose-dependent manner in lung tissue by LPS.The study showed that the anti-inflammatory and the protective affect of valnemulin againstacute lung injury may be through inhibited the expression of TLR4and CD14in LPS signalingpathway.