Oxidative stress generated during @entity63 /reperfusion injury has been shown to augment cellular responsiveness. Whereas oxidants are themselves known to induce several intracellular signaling cascades, their effect on signaling pathways initiated by other inflammatory stimuli remains poorly elucidated. Previous work has suggested that oxidants are able to prime alveolar macrophages for increased @entity1991 translocation in response to treatment with lipopolysaccharide (LPS). Because oxidants are known to stimulate the @entity19640 family of tyrosine kinases, we hypothesized that the oxidants might contribute to augmented @entity1991 translocation by LPS via the involvement of @entity19640 family kinases. To model macrophage priming in vitro, the @entity19 macrophage cell line, RAW 264.7, was first incubated with various oxidants and then exposed to low dose LPS. These studies show that oxidant stress is able to augment macrophage responsiveness to LPS as evidenced by earlier and increased @entity1991 translocation. Inhibition of the @entity19640 family kinases by either pharmacological inhibition using @entity29687 or through a molecular approach by cell transfection with @entity45072 was found to prevent the augmented LPS-induced @entity1991 translocation caused by oxidants. Interestingly, while @entity19640 kinase inhibition was able to prevent the LPS-induced @entity1991 translocation in oxidant-treated macrophages, this strategy had no effect on @entity1991 translocation caused by LPS in the absence of oxidants. These findings suggested that oxidative stress might divert LPS signaling along an alternative signaling pathway. Further studies demonstrated that the @entity19640 -dependent pathway induced by oxidant pretreatment involved the activation of phosphatidylinositol 3-kinase. Involvement of this pathway appeared to be independent of traditional LPS signaling. Together, these studies provide a novel potential mechanism whereby oxidants might prime alveolar macrophages for altered responsiveness to subsequent inflammatory stimuli and suggest different cellular targets for immunomodulation following @entity63 /reperfusion.

Oxidative stress reprograms lipopolysaccharide signaling via XXXX kinase-dependent pathway in RAW 264.7 macrophage cell line.

@entity29687 :: ('18169(Tax:10090)', 'Gene') :: ['PP2'] @entity1991 :: ('18033(Tax:10090)', 'Gene') :: ['NF-kappa B'] @entity19640 :: ('20779(Tax:10090)', 'Gene') :: ['Src'] @entity63 :: ('MESH:D007511', 'Disease') :: ['ischemia'] @entity19 :: ('10090', 'Species') :: ['murine'] @entity45072 :: ('12988(Tax:10090)', 'Gene') :: ['Csk']
@entity19640 :: (20779(Tax:10090),Gene) :: ['Src']
