PMID- 22687405 OWN - NLM STAT- MEDLINE DCOM- 20121015 LR - 20190720 IS - 1347-5215 (Electronic) IS - 0918-6158 (Linking) VI - 35 IP - 5 DP - 2012 TI - Mizoribine suppresses proliferation of rat glomerular epithelial cells in culture and inhibits increase of monocyte chemoattractant protein-1 and macrophage inflammatory protein-2 stimulated by thrombin. PG - 705-8 AB - Glomerular crescents play an important role in progressive glomerular injury. The lesions consist of epithelial cells, macrophages and fibrin deposition. Macrophage chemoattractant protin-1 (MCP-1) is a chemoattractant of monocytes, which has a potential of procoagulant activity. Macrophage inflammatory protein-2 (MIP-2) is a chemoattractant of neutrophils and acute necrotizing injury is primarily mediated by neutrophils in crescentic glomerulonephritis. Mizoribine (MZR) is an immunosuppressive drug and it has been used for organ transplantation and treatment of various autoimmune diseases. The aim of this study is to investigate the effects of MZR on glomerular epithelial cells (GEC). Rat GEC were cultured with K1 medium and used from 12th to 14th passage. GEC proliferation was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. MCP-1 and MIP-2 were quantified by enzyme-linked immunosorbent assay (ELISA) in culture supernatants and mRNA expressions of MCP-1 and MIP-2 were analyzed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR). The proliferation of GEC was suppressed by MZR in a dose-dependent manner in the range of 1.0-100.0 microg/mL. These concentrations of MZR had no toxic effect to GEC. Thrombin (1.0-5.0 U/mL) enhanced the production of MCP-1, MIP-2 and the mRNA expressions of MCP-1 and MIP-2. The stimulatory effect of thrombin was inhibited by addition of MZR (10 microg/mL). It is concluded that MZR may be useful for the treatment of crescentic glomerulonephritis. FAU - Yamabe, Hideaki AU - Yamabe H AD - Department of Nephrology, Graduate School of Medicine, Hirosaki University, Japan. yamabe@cc.hirosaki-u.ac.jp FAU - Shimada, Michiko AU - Shimada M FAU - Murakami, Reiichi AU - Murakami R FAU - Fujita, Takeshi AU - Fujita T FAU - Shimaya, Yuko AU - Shimaya Y FAU - Nakamura, Norio AU - Nakamura N LA - eng PT - Journal Article PL - Japan TA - Biol Pharm Bull JT - Biological & pharmaceutical bulletin JID - 9311984 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Chemokine CCL2) RN - 0 (Chemokine CXCL2) RN - 0 (Immunosuppressive Agents) RN - 0 (RNA, Messenger) RN - 0 (Ribonucleosides) RN - 4JR41A10VP (mizoribine) RN - EC 3.4.21.5 (Thrombin) SB - IM MH - Animals MH - Anti-Inflammatory Agents/pharmacology/therapeutic use MH - Cattle MH - Cell Proliferation/*drug effects MH - Chemokine CCL2/genetics/*metabolism MH - Chemokine CXCL2/genetics/*metabolism MH - Dose-Response Relationship, Drug MH - Epithelial Cells/cytology/*drug effects/metabolism MH - Glomerulonephritis/drug therapy/metabolism/pathology MH - Immunosuppressive Agents/pharmacology/therapeutic use MH - Kidney Glomerulus/cytology/*drug effects/metabolism MH - Male MH - RNA, Messenger/metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Reverse Transcriptase Polymerase Chain Reaction MH - Ribonucleosides/*pharmacology/therapeutic use MH - Thrombin/*pharmacology EDAT- 2012/06/13 06:00 MHDA- 2012/10/16 06:00 CRDT- 2012/06/13 06:00 PHST- 2012/06/13 06:00 [entrez] PHST- 2012/06/13 06:00 [pubmed] PHST- 2012/10/16 06:00 [medline] AID - JST.JSTAGE/bpb/35.705 [pii] AID - 10.1248/bpb.35.705 [doi] PST - ppublish SO - Biol Pharm Bull. 2012;35(5):705-8. doi: 10.1248/bpb.35.705.