Gene interactions and pathways from curated databases and text-mining
Biochem Biophys Res Commun 2006, PMID: 16870145

TLR4-NOX4-AP-1 signaling mediates lipopolysaccharide-induced CXCR6 expression in human aortic smooth muscle cells.

Patel, Devang N; Bailey, Steven R; Gresham, John K; Schuchman, David B; Shelhamer, James H; Goldstein, Barry J; Foxwell, Brian M; Stemerman, Michael B; Maranchie, Jodi K; Valente, Anthony J; Mummidi, Srinivas; Chandrasekar, Bysani

CXCL16 is a transmembrane non-ELR CXC chemokine that signals via CXCR6 to induce aortic smooth muscle cell (ASMC) proliferation. While bacterial lipopolysaccharide (LPS) has been shown to stimulate CXCL16 expression in SMC, its effects on CXCR6 are not known. Here, we demonstrate that LPS upregulates CXCR6 mRNA, protein, and surface expression in human ASMC. Inhibition of TLR4 with neutralizing antibodies or specific siRNA interference blocked LPS-mediated CXCR6 expression. LPS stimulated both AP-1 (c-Fos, c-Jun) and NF-kappaB (p50 and p65) activation, but only inhibition of AP-1 attenuated LPS-induced CXCR6 expression. Using dominant negative expression vectors and siRNA interference, we demonstrate that LPS induces AP-1 activation via MyD88, TRAF6, ERK1/2, and JNK signaling pathways. Furthermore, the flavoprotein inhibitor diphenyleniodonium chloride significantly attenuated LPS-mediated AP-1-dependent CXCR6 expression, as did inhibition of NOX4 NADPH oxidase by siRNA. Finally, CXCR6 knockdown inhibited CXCL16-induced ASMC proliferation. These results demonstrate that LPS-TLR4-NOX4-AP-1 signaling can induce CXCR6 expression in ASMC, and suggest that the CXCL16-CXCR6 axis may be an important proinflammatory pathway in the pathogenesis of atherosclerosis.

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Text Mining Data

CXCR6 → TLR4-NOX4-AP-1: " TLR4-NOX4-AP-1 signaling mediates lipopolysaccharide induced CXCR6 expression in human aortic smooth muscle cells "

CXCR6 → TLR4-NOX4-AP-1: " TLR4-NOX4-AP-1 signaling mediates lipopolysaccharide induced CXCR6 expression in human aortic smooth muscle cells "

CXCR6 → TLR4-NOX4-AP-1: " TLR4-NOX4-AP-1 signaling mediates lipopolysaccharide induced CXCR6 expression in human aortic smooth muscle cells "

CXCR6 → TLR4: " Inhibition of TLR4 with neutralizing antibodies or specific siRNA interference blocked LPS mediated CXCR6 expression "

CXCR6 → LPS: " Inhibition of TLR4 with neutralizing antibodies or specific siRNA interference blocked LPS mediated CXCR6 expression "

CXCR6 ⊣ LPS: " LPS stimulated both AP-1 ( c-Fos, c-Jun ) and NF-kappaB ( p50 and p65 ) activation, but only inhibition of AP-1 attenuated LPS induced CXCR6 expression "

CXCR6 → AP-1: " LPS stimulated both AP-1 ( c-Fos, c-Jun ) and NF-kappaB ( p50 and p65 ) activation, but only inhibition of AP-1 attenuated LPS induced CXCR6 expression "

AP-1 → LPS: " LPS stimulated both AP-1 ( c-Fos, c-Jun ) and NF-kappaB ( p50 and p65 ) activation, but only inhibition of AP-1 attenuated LPS induced CXCR6 expression "

NF-kappaB → AP-1: " LPS stimulated both AP-1 ( c-Fos, c-Jun ) and NF-kappaB ( p50 and p65 ) activation, but only inhibition of AP-1 attenuated LPS induced CXCR6 expression "

NF-kappaB → LPS: " LPS stimulated both AP-1 ( c-Fos, c-Jun ) and NF-kappaB ( p50 and p65 ) activation, but only inhibition of AP-1 attenuated LPS induced CXCR6 expression "

AP-1 → LPS: " Using dominant negative expression vectors and siRNA interference, we demonstrate that LPS induces AP-1 activation via MyD88, TRAF6, ERK1/2, and JNK signaling pathways "

CXCR6 → AP-1: " Furthermore, the flavoprotein inhibitor diphenyleniodonium chloride significantly attenuated LPS mediated AP-1 dependent CXCR6 expression, as did inhibition of NOX4 NADPH oxidase by siRNA "

CXCR6 → LPS: " Furthermore, the flavoprotein inhibitor diphenyleniodonium chloride significantly attenuated LPS mediated AP-1 dependent CXCR6 expression, as did inhibition of NOX4 NADPH oxidase by siRNA "

LPS-TLR4-NOX4-AP-1 → CXCR6: " These results demonstrate that LPS-TLR4-NOX4-AP-1 signaling can induce CXCR6 expression in ASMC, and suggest that the CXCL16-CXCR6 axis may be an important proinflammatory pathway in the pathogenesis of atherosclerosis "

CXCR6 → LPS-TLR4-NOX4-AP-1: " These results demonstrate that LPS-TLR4-NOX4-AP-1 signaling can induce CXCR6 expression in ASMC, and suggest that the CXCL16-CXCR6 axis may be an important proinflammatory pathway in the pathogenesis of atherosclerosis "

CXCR6 → LPS-TLR4-NOX4-AP-1: " These results demonstrate that LPS-TLR4-NOX4-AP-1 signaling can induce CXCR6 expression in ASMC, and suggest that the CXCL16-CXCR6 axis may be an important proinflammatory pathway in the pathogenesis of atherosclerosis "

CXCR6 → LPS-TLR4-NOX4-AP-1: " These results demonstrate that LPS-TLR4-NOX4-AP-1 signaling can induce CXCR6 expression in ASMC, and suggest that the CXCL16-CXCR6 axis may be an important proinflammatory pathway in the pathogenesis of atherosclerosis "

Manually curated Databases

  • OpenBEL Selventa BEL large corpus: CXCR6 (increases, CXCR6 Activity)
    Evidence: LPS stimulated both AP-1 (c-Fos, c-Jun) and NF-kappaB (p50 and p65) activation, but only inhibition of AP-1 attenuated LPS-induced CXCR6 expression
  • OpenBEL Selventa BEL large corpus: O/- complex () (increases, Activity)
    Evidence: LPS stimulated both AP-1 (c-Fos, c-Jun) and NF-kappaB (p50 and p65) activation, but only inhibition of AP-1 attenuated LPS-induced CXCR6 expression