CAV-1Enhances The Inflammatory Response Of Hyperoxia Mice By TLR4/ERK/NF-κb Signal Pathway

ObjectiveAlthough the high oxygen has been widely used in clinical treatment to patients with ICU, the accumulation of reactive oxygen species may cause the damage of lung.CAV-1is the principal structural component of caveolae. Cav-1regulates critical cell functions including proliferation, apoptosis, cell differentiation, transcytosis via diverse signaling pathways and inflammatory response. Although recent studies have shown that the CAV-1had a limited effect in side effects of high oxygen toxicity, the molecular mechanism of its high oxygen inflammation remains unclear. In this experiment, we study the impacts of CAV-1in hyperoxia-inflammation by TLR4/ERK/NF-κB signal pathway, to explore its role in the lung injury of hyperoxia-induced in the pathogenesis. MethodsWe studied the lung damage of hyperoxia by using CAV-1knockout (KO) mice, and established the cell and animal model by high oxygen of CAV-1KO and WT mice. We detected the expression of inflammatory cytokines (IL-6and TNF-) by ELISA in WT and cavl KO mice; detected the expression of TNF-and IL-6in WT and cavl KO mouse lung cells by Western blot; detected the factor of TLR4/ERK/NF-κB by indirect immunofluorescence staining and confocal microscopy imaging, NBT, H2DCF, lipid peroxidation, MPO; analyzed the lung histopathology by HE staining in WT and CAV-1KO mouse.ResultCompared with the WT mice, the expression of ROS and inflammatory cytokines (IL-6and TNF-) of CAV-1KO mice in conditions of high oxygen were lower (P<0.05). Furthermore, the hyperoxia-induced inflammation was regulated by CAV-1through the pattern recognition receptor(LPS, TLR4). Gene silencing siRNA down-regulated by CAV-1or expression of TLR4, will reduce ERK1/2phosphorylation and NF-κB, inhibition of NF-κB in mouse epithelial MLE-12cells were transferred, thus reducing the production of cytokines.Conclution(1) Compared with WT mice, the expression of ROS and inflammatory cytokines (IL-6and TNF-) was lower in conditions of high oxygen in CAV-1KO mice (P<0.05);(2) The hyperoxia-induced inflammation was regulated by CAV-1through the interaction pattern recognition receptor of LPS, TLR4;(3) The phosphorylation of ERK1/2and NF-κB was reduced by si RNA to knock down the expression of CAV-1or TLR4, and inhibition the tranfer of NF-κB in MLE-12cells of mouse, and then reducing the production of cytokines.