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An endothelial TLR4-VEGFR2 pathway mediates lung protection against oxidant-induced injury


, : An endothelial TLR4-VEGFR2 pathway mediates lung protection against oxidant-induced injury. Faseb Journal 30(3): 1317-1327

TLR4 deficiency causes hypersusceptibility to oxidant-induced injury. We investigated the role of TLR4 in lung protection, using used bone marrow chimeras; cell-specific transgenic modeling; and lentiviral delivery in vivo to knock down or express TLR4 in various lung compartments; and lung-specific VEGF transgenic mice to investigate the effect of TLR4 on VEGF-mediated protection. C57/BL6 mice were exposed to 100% oxygen in an enclosed chamber and assessed for survival and lung injury. Primary endothelial cells were stimulated with recombinant VEGF and exposed to hyperoxia or hydrogen peroxide. Endothelium-specific expression of human TLR4 (as opposed to its expression in epithelium or immune cells) increased the survival of TLR4-deficent mice in hyperoxia by 24 h and decreased LDH release and lung cell apoptosis after 72 h of exposure by 30%. TLR4 expression was necessary and sufficient for the protective effect of VEGF in the lungs and in primary endothelial cells in culture. TLR4 knockdown inhibited VEGF signaling through VEGF receptor 2 (VEGFR2), Akt, and ERK pathways in lungs and primary endothelial cells and decreased the availability of VEGFR2 at the cell surface. These findings demonstrate a novel mechanism through which TLR4, an innate pattern receptor, interacts with an endothelial survival pathway.

US$19.90

PMID: 26655705

DOI: 10.1096/fj.15-275024


Other references

Myers, R.B., 1978: Practical system for validating heat sterilization processes. Journal of the Parenteral Drug Association 32(5): 216-225

Wongchanapai, W.; Tsang, B.K.; He, Z.; Ho, I.K., 1998: Relative involvement of spinal opioid receptors in physical dependence on intrathecal butorphanol and morphine. The present study was carried out to investigate the relative involvement of spinal opioid receptors in the development of physical dependence on intrathecal (IT) butorphanol in comparison with IT morphine. Dependence was induced by continuous IT...

Jiang, H.; Tong, T.; Sun, J.; Xu, Y.; Zhao, Z.; Liao, D., 2014: Purification and characterization of antioxidative peptides from round scad (Decapterus maruadsi) muscle protein hydrolysate. Muscle protein from round scad (Decapterus maruadsi) was hydrolyzed with five commercial proteases, namely, Alcalase, neutral protease, papain, pepsin, and trypsin. Round scad hydrolysate (RSH) prepared with Alcalase demonstrated high antioxidativ...

WangZhenHai; HongHuanYu; WangHai(etal), 2008: Experimental study of biological membrane in prevention of adhesion of tendon. A study was conducted to investigate the effect of Zhenghai biological membrane on the prevention of tendon adhesion. Eighteen chickens were divided into 2 groups. Zhenghai biological membrane was used in the experimental group while simple Kessle...

Baker, B.S.; Wolfner, M.F., 1988: A molecular analysis of doublesex, a bifunctional gene that controls both male and female sexual differentiation in Drosophila melanogaster. The doublesex (dsx) gene regulates somatic sexual differentiation in both sexes in Drosophila melanogaster. dsx has active but opposite negative regulatory functions in males and females. In males, the dsx locus represses the genes responsible for...

Nguyen, L.Nam.; Bormann, Jörg.; Le, G.Thi.Thu.; Stärkel, C.; Olsson, S.; Nosanchuk, J.D.; Giese, H.; Schäfer, W., 2011: Autophagy-related lipase FgATG15 of Fusarium graminearum is important for lipid turnover and plant infection. Autophagy is a non-selective degradation pathway in eukaryotic cells that is conserved from yeasts to humans. Autophagy is involved in the virulence of several pathogenic fungi such as Magnaporthe grisea or Colletotrichum orbiculare. In the curren...

Simcock, N.Kay., 2016: Love is in the air: Sticklebacks' choice of mate depends on dissolved oxygen levels. Evolution; International Journal of Organic Evolution: -

Wu, H-Chin.; Chang, C-Hsiang.; Ke, H-Lung.; Chang, W-Shin.; Cheng, H-Ni.; Lin, H-Hui.; Wu, C-Yu.; Tsai, C-Wen.; Tsai, R-Yin.; Lo, W-Chung.; Bau, D-Tian., 2011: Association of cyclooxygenase 2 polymorphic genotypes with prostate cancer in taiwan. The aim of this study was to evaluate the association of polymorphic genotypes in the cyclooxygenase 2 gene (COX2), which is reported to be overexpressed in prostate tumors, with Taiwan prostate cancer patients. Six polymorphic variants of COX2 we...

Crawford, J.S., 1969: Nature of fascia lata and its fate after implantation. American Journal of Ophthalmology 67(6): 900-907

Chanet, M., 1976: Reception of oil grains in storage units. First Quarter 62 3-19