TLR4 signaling induces TLR2 expression in endothelial cells via neutrophil NADPH oxidase
AUTOR(ES)
Fan, Jie
FONTE
American Society for Clinical Investigation
RESUMO
Interactions of polymorphonuclear neutrophils (PMNs) with endothelial cells may contribute to the activation of endothelial cell responses involved in innate immunity. We explored a novel function of PMN NADPH oxidase in the mechanism of Toll-like receptor-2 (TLR2) upregulation induced by LPS-TLR4 signaling in endothelial cells. We showed that LPS induced TLR2 up-regulation through TLR4- and MyD88-dependent signaling. In neutropenic mice, the LPS-induced NF-kB activation and TLR2 expression were significantly reduced, and both responses were restored upon repletion by PMN obtained from WT mice but not by PMNs from NADPH oxidase gp91phox–/– mice. These findings were recapitulated in mouse lung vascular endothelial cells cocultured with PMNs, indicating that the augmented NF-kB activation and the resultant TLR2 upregulation in endothelial cells were secondary to oxidant signaling generated by PMN NADPH oxidase. The functional relevance of NADPH oxidase in mediating TLR4-induced TLR2 expression in endothelial cells was evident by markedly elevated and stable ICAM-1 expression as well as augmented PMN migration in response to sequential challenge with LPS and peptidoglycan. Thus, PMN NADPH oxidase–derived oxidant signaling is an important determinant of the cross talk between TLR4 and TLR2 and the control of endothelial cell activation.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=213490Documentos Relacionados
- Role of TLR2 and TLR4 on human neutrophil functions against Paracoccidioides brasiliensis
- TLR2 and TLR4 mediated host immune responses in major infectious diseases: a review
- Expressão de TLR2 e TLR4 em lesões de pacientes com leishmaniose tegumentar americana
- Different engagement of TLR2 and TLR4 in Porphyromonas gingivalis vs. ligature-induced periodontal bone loss
- Avaliação do papel dos receptores TLR2 e TLR4 na produção de citocinas por fibroblastos humanos periodontais deficientes desses receptores