alpha V beta 3-integrin expression through ERK activation mediates cell attachment and is necessary for production of tumor necrosis factor alpha in monocytic THP-1 cells stimulated by phorbol myristate acetate

Macrophages play a key role in inflammation. Activated macrophages express adhesion molecules and produce tumor necrosis factor alpha (TNF alpha). Integrins are the main adhesion molecules that mediate binding to the extracellular matrix and they are involved in intracellular pathways. In the present study, human monocytic THP-1 cell adhesion to uncoated plastic plate was examined to investigate the regulatory mechanism of TNF alpha secretion. Addition of phorbol myristate acetate (PMA) for THP-1 cell activation induced cell adhesion in parallel with TNF alpha production. Among the mitogen-activated protein kinase pathways, the protein kinase C (PKC)-extracellular signal-regulated kinase (ERK) pathway was involved in alpha V beta 3-integrin expression and PMA-induced cell adhesion. Flow cytometry and reverse transcription quantitative polymerase chain reaction analysis revealed increased expression of matrix-binding integrins including integrin-alpha V beta 3. Blockade of alpha V beta 3-integrin by a specific antibody suppressed cell adhesion and TNF alpha production. These findings indicate that TNF alpha production from THP-1 cells is PKC-ERK, alpha V beta 3-integrin and adhesion-dependent and its related pathway could be a target for TNF alpha-related diseases. (C) 2011 Elsevier Inc. All rights reserved.