Synergistic induction of monocyte chemoattractant protein-1 (MCP-1) by platelet-derived growth factor and interleukin-1.
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-1 beta (IL-1 beta), which induced a long lasting elevation of MCP-1 mRNA for more than 20 h. Together, PDGF and IL-1 beta 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-1 beta-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-1 beta: 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.
Goppelt-Struebe
M
M
Medizinische Klinik IV, Universität Erlangen-Nürnberg, Germany.
Stroebel
M
M
D000818:Animals; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics*; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004355:Drug Stability; D004357:Drug Synergism; D015870:Gene Expression / Q000187:drug effects*; D005920:Glomerular Mesangium / Q000378:metabolism; D006207:Half-Life; D007375:Interleukin-1 / Q000494:pharmacology*; D007700:Kinetics; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D012701:Serotonin / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D018932:Chemokine CCL2; D007375:Interleukin-1; D010982:Platelet-Derived Growth Factor; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D003609:Dactinomycin; D012701:Serotonin; D003513:Cycloheximide