Synergistic induction of monocyte chemoattractant protein-1 (MCP-1) by platelet-derived growth factor and interleukin-1

Abstract

Monocyte chemoattractant protein-1 (MCP-1) plays an important role in the recruitment of monocytic cells to the site of inflammation. Resting mesangial cells express barely detectable levels of MCP-1 mRNA. Treatment of rat mesangial cells with platelet products PDGF-AB, PDGF-BB or serotonin transiently induced MCP-1 expression with a maximum after 2 to 4 h and a decline to baseline after 6 to 8 h. Different kinetics were observed with interleukin-1β (IL-1β), which induced a long lasting elevation of MCP-1 mRNA for more than 20 h. Together, PDGF and IL-1β synergistically induced MCP-1 expression. The effect was most obvious after 16 to 20 h, when induction by PDGF alone had already faded, but still PDGF strongly enhanced IL-1β-induced MCP-1 mRNA expression. MCP-1 mRNA levels were regulated by changes in the stability of the mRNA: inhibition of protein synthesis by cycloheximide by itself induced MCP-1 mRNA expression and led to superinduction in the presence of PDGF. Message stabilization also contributed to the synergistic action of PDGF and IL-1β: the apparent half life of MCP-1 mRNA determined in the presence of actinomycin D was prolonged when both stimuli were added together. We could thus show that in mesangial cells different types of cytokines and growth factors synergize to enhance MCP-1, the secretion of which could lead to the recruitment of monocytic cells into the inflamed mesangium.