TY - JOUR
T1 - Production and regulation of monocyte chemoattractant protein-1 in lipopolysaccharide- or monosodium urate crystal-induced arthritis in rabbits
T2 - Roles of tumor necrosis factor α, interleukin-1, and interleukin-8
AU - Matsukawa, Akihiro
AU - Miyazaki, Shinichi
AU - Maeda, Takako
AU - Tanase, Sumio
AU - Feng, Lili
AU - Ohkawara, Susumu
AU - Yoshinaga, Masaru
AU - Yoshimura, Teizo
PY - 1998/8/1
Y1 - 1998/8/1
N2 - The production of monocyte chemoattractant protein-1 (MCP-1) and its regulation by TNFα, IL-1, and IL-8 were investigated in two rabbit models of arthritis induced by intra-articular injection of lipopolysaccharide (LPS) or monosodium urate (MSU) crystals. We first prepared recombinant rabbit MCP-1 and antibodies and then developed an immunoassay. The immunoassay detected 3 pg/ml rabbit MCP-1 and did not cross-react with other rabbit chemokines such as IL-8 or GRO. MCP-1 was first detected in synovial fluid (SF) at 1 hour, and peaked at 4 or 2 hours after the injection of LPS or MSU crystals, respectively. Immunohistochemically, MCP-1 was detected in synovial lining cells and infiltrating neutrophils. The amounts of MCP-1 detected in SF from neutrophil-depleted rabbits were similar to those in normal rabbits, suggesting that synovial lining cells were the main source of MCP-1 detected in SF. The peak level of MCP-1 in SF after LPS-injection was inhibited by 57% with anti-TNFα mAb and by 41% with IL-1 receptor antagonist (IL-1Ra). Coadministration of anti-TNFα mAb and IL-1Ra inhibited 90% of MCP-1 production. In contrast, the peak level of MCP-1 in SF after MSU crystal- injection was not affected by any cytokine inhibitor, but was reduced by 52% with coadministration of anti-TNFα mAb and IL-1Ra. Anti-IL-8 IgG had no effect on the production of MCP-1 in either model. Thus, the production of MCP-1 in LPS-induced arthritis was mostly regulated by TNFα and IL-1, whereas half the extent of MCP-1 production in MSU crystal-induced arthritis was independent of TNFα or IL-1. IL-8 does not seem to regulate the production of MCP-1 in SF either directly or indirectly. Finally, administration of neutralizing anti-MCP-1 antibody inhibited LPS- and MSU crystal-induced monocyte infiltration by 58.4% and 44.9%, respectively, suggesting that synovial production of MCP-1 plays an important role in the recruitment of monocytes in these arthritis models.
AB - The production of monocyte chemoattractant protein-1 (MCP-1) and its regulation by TNFα, IL-1, and IL-8 were investigated in two rabbit models of arthritis induced by intra-articular injection of lipopolysaccharide (LPS) or monosodium urate (MSU) crystals. We first prepared recombinant rabbit MCP-1 and antibodies and then developed an immunoassay. The immunoassay detected 3 pg/ml rabbit MCP-1 and did not cross-react with other rabbit chemokines such as IL-8 or GRO. MCP-1 was first detected in synovial fluid (SF) at 1 hour, and peaked at 4 or 2 hours after the injection of LPS or MSU crystals, respectively. Immunohistochemically, MCP-1 was detected in synovial lining cells and infiltrating neutrophils. The amounts of MCP-1 detected in SF from neutrophil-depleted rabbits were similar to those in normal rabbits, suggesting that synovial lining cells were the main source of MCP-1 detected in SF. The peak level of MCP-1 in SF after LPS-injection was inhibited by 57% with anti-TNFα mAb and by 41% with IL-1 receptor antagonist (IL-1Ra). Coadministration of anti-TNFα mAb and IL-1Ra inhibited 90% of MCP-1 production. In contrast, the peak level of MCP-1 in SF after MSU crystal- injection was not affected by any cytokine inhibitor, but was reduced by 52% with coadministration of anti-TNFα mAb and IL-1Ra. Anti-IL-8 IgG had no effect on the production of MCP-1 in either model. Thus, the production of MCP-1 in LPS-induced arthritis was mostly regulated by TNFα and IL-1, whereas half the extent of MCP-1 production in MSU crystal-induced arthritis was independent of TNFα or IL-1. IL-8 does not seem to regulate the production of MCP-1 in SF either directly or indirectly. Finally, administration of neutralizing anti-MCP-1 antibody inhibited LPS- and MSU crystal-induced monocyte infiltration by 58.4% and 44.9%, respectively, suggesting that synovial production of MCP-1 plays an important role in the recruitment of monocytes in these arthritis models.
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M3 - Article
C2 - 9714185
AN - SCOPUS:0031849593
VL - 78
SP - 973
EP - 985
JO - Laboratory Investigation
JF - Laboratory Investigation
SN - 0023-6837
IS - 8
ER -