Journal Article

Thrombin enhances the production of monocyte chemoattractant protein-1 and macrophage inflammatory protein-2 in cultured rat glomerular epithelial cells

Takeshi Fujita, Hideaki Yamabe, Michiko Shimada, Reiichi Murakami, Ryuichiro Kumasaka, Norio Nakamura, Hiroshi Osawa and Ken Okumura

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 23, issue 11, pages 3412-3417
Published in print November 2008 | ISSN: 0931-0509
Published online July 2008 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/gfn352
Thrombin enhances the production of monocyte chemoattractant protein-1 and macrophage inflammatory protein-2 in cultured rat glomerular epithelial cells

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Background. Glomerular crescents play an important role in progressive glomerular injury. The lesions consist of epithelial cells, macrophages and deposits of fibrin and extracellular matrix. Monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-2 (MIP-2) are members of chemokine subfamilies. MCP-1 and MIP-2 are potent chemoattractant leukocyte cytokines, and they may be involved in crescent formation. Thrombin participates in fibrin formation. We hypothesized that thrombin stimulates the production of MCP-1 and MIP-2 by glomerular epithelial cells (GECs).

Methods. Cultured rat GECs from the 19th to the 24th passage were used. We incubated GECs with or without thrombin to examine the effect of thrombin on the production of MCP-1 and MIP-2. The levels of MCP-1 and MIP-2 were measured in the cell supernatants by enzyme-linked immunosorbent assay (ELISA). The mRNA expressions of MCP-1 and MIP-2 were analysed by real-time reverse transcriptase–polymerase chain reaction (RT-PCR). We also examined the inhibitory effect of argatroban, a synthetic thrombin inhibitor, and prednisolone in the production of MCP-1 and MIP-2 stimulated by thrombin.

Results. Thrombin stimulated the production of MCP-1 and MIP-2 in a dose- and time-dependent manner. Thrombin also enhanced the mRNA expressions of MCP-1 and MIP-2 in the GECs. The stimulating effect of thrombin on the production of MCP-1 and MIP-2 was inhibited by the addition of argatroban or prednisolone.

Conclusions. We demonstrated a novel role of thrombin: it stimulates the production of MCP-1 and MIP-2 by GECs. It is clinically important that the inhibition of these chemokines leads to the improvement of crescentic glomerulonephritis. Anti-thrombin drugs and prednisolone may be useful in treating crescentic glomerulonephritis.

Keywords: GEC; MCP-1; MIP-2; thrombin

Journal Article.  3112 words.  Illustrated.

Subjects: Nephrology

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