Production and regulation of monocyte chemoattractant protein-1 in lipopolysaccharide- or monosodium urate crystal-induced arthritis in rabbits: Roles of tumor necrosis factor α, interleukin-1, and interleukin-8

Akihiro Matsukawa, Shinichi Miyazaki, Takako Maeda, Sumio Tanase, Lili Feng, Susumu Ohkawara, Masaru Yoshinaga, Teizo Yoshimura

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Abstract

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.

Original languageEnglish
Pages (from-to)973-985
Number of pages13
JournalLaboratory Investigation
Volume78
Issue number8
Publication statusPublished - Aug 1998
Externally publishedYes

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Chemokine CCL2
Uric Acid
Interleukin-8
Interleukin-1
Lipopolysaccharides
Tumor Necrosis Factor-alpha
Rabbits
Synovial Fluid
Interleukin-1 Receptors
Arthritis
Crystal Arthropathies
Immunoassay
Injections
Monocytes
Neutrophils
Intra-Articular Injections
Antibodies
Chemokines

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Production and regulation of monocyte chemoattractant protein-1 in lipopolysaccharide- or monosodium urate crystal-induced arthritis in rabbits : Roles of tumor necrosis factor α, interleukin-1, and interleukin-8. / Matsukawa, Akihiro; Miyazaki, Shinichi; Maeda, Takako; Tanase, Sumio; Feng, Lili; Ohkawara, Susumu; Yoshinaga, Masaru; Yoshimura, Teizo.

In: Laboratory Investigation, Vol. 78, No. 8, 08.1998, p. 973-985.

Research output: Contribution to journalArticle

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abstract = "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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AU - Miyazaki, Shinichi

AU - Maeda, Takako

AU - Tanase, Sumio

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AU - Ohkawara, Susumu

AU - Yoshinaga, Masaru

AU - Yoshimura, Teizo

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