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Am J Physiol Lung Cell Mol Physiol 288: L307-L316, 2005. First published October 15, 2004; doi:10.1152/ajplung.00105.2004
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VCAM-1 upregulation via PKC{delta}-p38 kinase-linked cascade mediates the TNF-{alpha}-induced leukocyte adhesion and emigration in the lung airway epithelium

Chang-Hoon Woo, Jae-Hyang Lim, and Jae-Hong Kim

School of Life Sciences and Biotechnology, Korea University, Seoul, Korea

Submitted 22 March 2004 ; accepted in final form 13 October 2004

Vascular cell adhesion molecule (VCAM)-1 plays a central role in the recruitment of inflammatory cells, and its expression is rapidly induced by proinflammatory cytokines such as TNF-{alpha}. In the present study, we show that pretreatment with rottlerin, a specific inhibitor of protein kinase C (PKC)-{delta}, or transient transfection with antisense PKC{delta} oligonucleotides significantly inhibits TNF-{alpha}-induced expression of VCAM-1, but not of intercellular adhesion molecule (ICAM)-1 in human lung epithelium A549 cells. In addition, TNF-{alpha} was shown to induce the expression of VCAM-1 in a p38 kinase-dependent manner; also, TNF-{alpha}-induced p38 kinase activation was blocked by inhibition of PKC{delta}, suggesting that p38 kinase is apparently situated downstream of PKC{delta} in the TNF-{alpha}-signaling pathway to VCAM-1 expression. Notably, inhibition of the PKC{delta}-p38 kinase cascade also attenuated the TNF-{alpha}-induced adhesion of neutrophils to lung epithelium and the trafficking of leukocytes across the epithelium into the airway lumen in vivo. Together, these findings indicate that signaling via PKC{delta}-p38 kinase-linked cascade specifically induces expression of VCAM-1 in lung epithelium in response to TNF-{alpha} and that this effect is both functionally and clinically significant.

lung inflammation; protein kinase C-{delta}; vascular cell adhesion molecule-1


Address for reprint requests and other correspondence: J.-H. Kim, School of Life Sciences and Biotechnology, Korea Univ., 5-1 Anam-dong, Sungbuk-gu, Seoul, 136-701, Korea. (E-mail: jhongkim{at}korea.ac.kr)




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