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

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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.

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