Investigation of the functional role played by the chemokine monocyte chemoattractant protein-1 in interleukin-1-induced murine peritonitis.
1. Intraperitoneal (i.p.) injection of murine recombinant IL-1beta (mrIL-1beta) produced a dose-dependent (0.5-50 ng) and time-related (0.5-2 h) secretion of murine monocyte chemoattractant protein-1 (mMCP-1; 3-4 ng per cavity) in the lavage fluids. MCP-1 mRNA could also be detected in the cell pellets by reverse transcriptase-polymerase chain reaction (RT-PCR). 2. MCP-1 levels were reduced by more than 90% by co-administration of IL-1 receptor antagonist (10 microg) (n=6, P<0.05). In contrast, an IL-1 mutant with low affinity for IL-1 receptor type I, termed yIL-1betadelta4 (50 ng), produced only a modest release of the chemokine. Treatment of mice with dexamethasone (DEX) (approximately 1 mg kg(-1) s.c.) reduced mrIL-1beta-induced mMCP-1 gene expression (apparent total inhibition) and protein release in the lavage fluids (approximately 40% reduction; n=10; P<0.05). Drastic reductions in the numbers of residential macrophages or mast cells did not modify the levels of mMCP-1 recovered in the lavage fluids. 3. Injection of mrIL-1beta produced neutrophil accumulation into the peritoneal cavities (maximal at 4 h with 1.42+/-0.15 x 10(6) cells per mouse). Co-injection of a specific polyclonal antibody against mMCP-1 reduced this process by more than 50% (n=6; P<0.05). In conclusion, we studied the mechanisms leading to the specific release of the CC chemokine mMCP-1 after in vivo administration of mrIL-1beta.
Ajuebor
M N
MN
Department of Biochemical Pharmacology, The William Harvey Research Institute, London.
Gibbs
L
L
Flower
R J
RJ
Das
A M
AM
Perretti
M
M
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000378:metabolism* / Q000502:physiology; D016207:Cytokines / Q000378:metabolism; D003907:Dexamethasone / Q000627:therapeutic use; D007375:Interleukin-1; D008297:Male; D051379:Mice; D010538:Peritonitis / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000893:Anti-Inflammatory Agents; D018932:Chemokine CCL2; D016207:Cytokines; D007375:Interleukin-1; D003907:Dexamethasone