PMID- 18622025
OWN - NLM
STAT- MEDLINE
DCOM- 20090302
LR  - 20201209
IS  - 1460-2385 (Electronic)
IS  - 0931-0509 (Linking)
VI  - 23
IP  - 11
DP  - 2008 Nov
TI  - Thrombin enhances the production of monocyte chemoattractant protein-1 and 
      macrophage inflammatory protein-2 in cultured rat glomerular epithelial cells.
PG  - 3412-7
LID - 10.1093/ndt/gfn352 [doi]
AB  - 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.
FAU - Fujita, Takeshi
AU  - Fujita T
AD  - Department of Nephrology, Hirosaki University Graduate School of Medicine, 
      Hirosaki, 036-8562, Japan. fuji-ta@cc.hirosaki-u.ac.jp
FAU - Yamabe, Hideaki
AU  - Yamabe H
FAU - Shimada, Michiko
AU  - Shimada M
FAU - Murakami, Reiichi
AU  - Murakami R
FAU - Kumasaka, Ryuichiro
AU  - Kumasaka R
FAU - Nakamura, Norio
AU  - Nakamura N
FAU - Osawa, Hiroshi
AU  - Osawa H
FAU - Okumura, Ken
AU  - Okumura K
LA  - eng
PT  - Journal Article
DEP - 20080712
PL  - England
TA  - Nephrol Dial Transplant
JT  - Nephrology, dialysis, transplantation : official publication of the European 
      Dialysis and Transplant Association - European Renal Association
JID - 8706402
RN  - 0 (Anticoagulants)
RN  - 0 (Ccl2 protein, rat)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemokine CXCL2)
RN  - 0 (Cxcl2 protein, rat)
RN  - 0 (Glucocorticoids)
RN  - 0 (Pipecolic Acids)
RN  - 0 (RNA, Messenger)
RN  - 0 (Sulfonamides)
RN  - 94ZLA3W45F (Arginine)
RN  - 9PHQ9Y1OLM (Prednisolone)
RN  - EC 3.4.21.5 (Thrombin)
RN  - IY90U61Z3S (argatroban)
SB  - IM
MH  - Animals
MH  - Anticoagulants/pharmacology
MH  - Arginine/analogs & derivatives
MH  - Cells, Cultured
MH  - Chemokine CCL2/*metabolism
MH  - Chemokine CXCL2/*metabolism
MH  - Glucocorticoids/pharmacology
MH  - Male
MH  - Pipecolic Acids/pharmacology
MH  - Podocytes/cytology/*metabolism
MH  - Prednisolone/pharmacology
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Sulfonamides
MH  - Thrombin/*physiology
EDAT- 2008/07/16 09:00
MHDA- 2009/03/03 09:00
CRDT- 2008/07/16 09:00
PHST- 2008/07/16 09:00 [pubmed]
PHST- 2009/03/03 09:00 [medline]
PHST- 2008/07/16 09:00 [entrez]
AID - gfn352 [pii]
AID - 10.1093/ndt/gfn352 [doi]
PST - ppublish
SO  - Nephrol Dial Transplant. 2008 Nov;23(11):3412-7. doi: 10.1093/ndt/gfn352. Epub 
      2008 Jul 12.