VCAM-1 upregulation via PKCδ-p38 kinase-linked cascade mediates the TNF-α-induced leukocyte adhesion and emigration in the lung airway epithelium

Chang Hoon Woo, Jae Hyang Lim, Jae Hong Kim

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

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-α. In the present study, we show that pretreatment with rottlerin, a specific inhibitor of protein kinase C (PKC)-δ, or transient transfection with antisense PKCδ oligonucleotides significantly inhibits TNF-α-induced expression of VCAM-1, but not of intercellular adhesion molecule (ICAM)-1 in human lung epithelium A549 cells. In addition, TNF-α was shown to induce the expression of VCAM-1 in a p38 kinase-dependent manner; also, TNF-α-induced p38 kinase activation was blocked by inhibition of PKCδ, suggesting that p38 kinase is apparently situated downstream of PKCδ in the TNF-α-signaling pathway to VCAM-1 expression. Notably, inhibition of the PKCδ-p38 kinase cascade also attenuated the TNF-α-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 PKCδ-p38 kinase-linked cascade specifically induces expression of VCAM-1 in lung epithelium in response to TNF-α and that this effect is both functionally and clinically significant.

Original languageEnglish
Pages (from-to)L307-L316
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume288
Issue number2 32-2
DOIs
Publication statusPublished - 2005 Feb

Keywords

  • Lung inflammation
  • Protein kinase C-δ
  • Vascular cell adhesion molecule-1

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

Fingerprint Dive into the research topics of 'VCAM-1 upregulation via PKCδ-p38 kinase-linked cascade mediates the TNF-α-induced leukocyte adhesion and emigration in the lung airway epithelium'. Together they form a unique fingerprint.

  • Cite this