The role and mechanism of K Ca 3.1 channels in human monocyte migration induced by palmitic acid
2018
Abstract
Monocytemigration into diseased tissues contributes to the pathogenesis of diseases. Intermediate-conductance Ca 2+ -activated K + (K Ca 3.1) channels play an important role in cell migration. However, the role of K Ca 3.1 channels in mediating
monocytemigration induced by palmitic acid (PA) is still unclear. Using cultured THP-1 cells and peripheral blood mononuclear cells from healthy subjects, we investigated the role and signaling mechanisms of K Ca 3.1 channels in mediating the migration induced by PA. Using methods of Western blotting analysis, RNA interference, cell migration assay and ELISA, we found that PA-treated
monocytesexhibited increment of the protein levels of K Ca 3.1 channel and
monocytechemoattractant protein-1 (MCP-1), and the effects were reversed by co-incubation of PA with anti-
TLR2/4 antibodies or by specific inhibitors of p38-MAPK, or NF-κB. In addition, PA increased
monocytemigration, which was abolished by a specific K Ca 3.1 channel blocker, TRAM-34, or K Ca 3.1 small interfering RNA (siRNA). The expression and secretion of MCP-1 induced by PA was also similarly prevented by TRAM-34 and K Ca 3.1 siRNA. These results demonstrate for the first time that PA upregulates K Ca 3.1 channels through
TLR2/4, p38-MAPK and NF-κB pathway to promote the expression of MCP-1, and then induce the trans-endothelial migration of
monocytes.
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