J Korean Assoc Oral Maxillofac Surg.  2007 Oct;33(5):445-454.

The role of mapk and pkc-delta in phosphatidic acid-mediated intercellular adhesion molecule-1 expression

• Cho WS
• Yoon HS
• Chin BR
• Baek SH

Abstract

BACKGROUND: Phosphatidic acid (PA), an important second messenger, is involved in inflammation. Notably, cell-cell interactions via adhesion molecules play a central role in inflammation. This thesis show that PA induces expression of intercellular adhesion molecule-1 (ICAM-1) on macrophages and describe the signaling pathways.
MATERIALS AND METHODS
Macrophages were cultured in the presence of 10% FBS and assayed cell to cell adhesion using HUVEC. For the gene and protein analysis, RT-PCR, Western blot and flow cytometry were performed. In addition, overexpressed cell lines for dominant negative PKC-delta mutant established and tested their effect on the promoter activity and expression of ICAM-1 protein by PA.
RESULTS
PA-activated macrophages significantly increased adhering to human umbilical vein endothelial cell and this adhesion was mediated by ICAM-1. Pretreatment with rottlerin (PKC-delta inhibitor) or expression of a dominant negative PKC-delta mutant, but not Go6976 (classical PKC-alpha inhibitor) and myristoylated PKC-zeta inhibitor, attenuated PA-induced ICAM-1 expression. The p38 mitogen-activated protein kinase (MAPK) inhibitor blocked PA-induced ICAM-1 expression in contrast, ERK upstream inhibitor didn't block ICAM-1.
CONCLUSION
These data suggest that PA-induced ICAM-1 expression and cell-cell adhesion in macrophages requires PKC-delta activation and that PKC-delta activation is triggers to sequential activation of p38 MAPK.

Keyword

Macrophage; ICAM-1; Adhesion; MAPK; Protein kinase C

MeSH Terms

Blotting, Western
Cell Adhesion
Cell Line
Endothelial Cells
Flow Cytometry
Humans
Inflammation
Intercellular Adhesion Molecule-1*
Macrophages
p38 Mitogen-Activated Protein Kinases
Phosphatidic Acids
Protein Kinase C
Protein Kinases
Second Messenger Systems
Umbilical Veins
Intercellular Adhesion Molecule-1
Phosphatidic Acids
Protein Kinase C
Protein Kinases
p38 Mitogen-Activated Protein Kinases