αVβ3-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 (TNFα). 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 TNFα secretion. Addition of phorbol myristate acetate (PMA) for THP-1 cell activation induced cell adhesion in parallel with TNFα production. Among the mitogen-activated protein kinase pathways, the protein kinase C (PKC)-extracellular signal-regulated kinase (ERK) pathway was involved in αVβ3-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-αVβ3. Blockade of αVβ3-integrin by a specific antibody suppressed cell adhesion and TNFα production. These findings indicate that TNFα production from THP-1 cells is PKC-ERK, αVβ3-integrin and adhesion-dependent and its related pathway could be a target for TNFα-related diseases.