PMID- 21156725
OWN - NLM
STAT- MEDLINE
DCOM- 20110426
LR  - 20161125
IS  - 1460-2350 (Electronic)
IS  - 0268-1161 (Linking)
VI  - 26
IP  - 2
DP  - 2011 Feb
TI  - Thrombin-induced chemokine production in endometrial stromal cells.
PG  - 407-13
LID - 10.1093/humrep/deq347 [doi]
AB  - BACKGROUND: In order to investigate the regulation of chemokines [interleukin-8 
      (IL-8), growth-regulated oncogene (GRO)alpha, monocyte chemoattractant protein-1 
      (MCP-1)) induced by thrombin in endometrial stromal cells (ESCs), the effects of 
      thrombin, a protease activated receptor (PAR)-1 antagonist (PPACK), 
      mitogen-activated protein kinase kinase inhibitor (U0126), phospholipase C 
      inhibitor (U-73122), an antagonist of the intracellular InsP3 receptor 
      (2-aminoethoxy-diphenylborate (2-APB)] and a protein kinase C inhibitor 
      (GF-109203X) on the production of chemokines by ESCs were evaluated. METHODS: 
      ESCs from eight endometrial specimens in the secretory phase were cultured and 
      incubated for 24h with thrombin and PPACK, U0126, U-73122, 2-APB or GF-109203X. 
      The levels of IL-8, GROalpha and MCP-1 in the culture medium were measured by means 
      of ELISA. The activation of MAP kinase was detected by western blot analysis 
      using anti-phosphorylated MAP kinase (ERK1/2) antibody. RESULTS: Following 
      stimulation by thrombin, the production of IL-8, GROalpha and MCP-1 increased 
      significantly in a dose-dependent manner. PPACK, U0126, U-73122, 2-APB or 
      GF-109203X suppressed the increases in production of IL-8, GROalpha and MCP-1 induced 
      by thrombin (P < 0.001, P <0.001 and P <0.001, respectively). MAP kinase 
      activities were induced by treatment with thrombin, and were suppressed by PPACK, 
      U0126, U-73122, 2-APB or GF-109203X. CONCLUSIONS: Our results suggest that 
      thrombin stimulates the production of IL-8, GROalpha and MCP-1 via PAR-1 by a 
      mechanism involving the MAP kinase system. The increases in IL-8, GROalpha and MCP-1 
      may contribute to the maintenance of implantation involving leukocyte chemotaxis.
FAU - Kawano, Yasushi
AU  - Kawano Y
AD  - Department of Obstetrics and Gynecology, Faculty of Medicine, Oita University, 
      1-1 Idaigaoka, Hasama, Yufu, Oita 879-5593, Japan. kawayas@oita-u.ac.jp
FAU - Furukawa, Yuichi
AU  - Furukawa Y
FAU - Kawano, Yukie
AU  - Kawano Y
FAU - Nasu, Kaei
AU  - Nasu K
FAU - Narahara, Hisashi
AU  - Narahara H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20101214
PL  - England
TA  - Hum Reprod
JT  - Human reproduction (Oxford, England)
JID - 8701199
RN  - 0 (Amino Acid Chloromethyl Ketones)
RN  - 0 (Boron Compounds)
RN  - 0 (Butadienes)
RN  - 0 (CXCL1 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemokine CXCL1)
RN  - 0 (Estrenes)
RN  - 0 (Indoles)
RN  - 0 (Interleukin-8)
RN  - 0 (Maleimides)
RN  - 0 (Nitriles)
RN  - 0 (Pyrrolidinones)
RN  - 0 (Receptor, PAR-1)
RN  - 0 (U 0126)
RN  - 112648-68-7 
      (1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione)
RN  - E4ES684O93 (2-aminoethoxydiphenyl borate)
RN  - EC 3.4.21.5 (Thrombin)
RN  - L79H6N0V6C (bisindolylmaleimide I)
RN  - N62UL02WW4 (phenylalanyl-prolyl-arginine-chloromethyl ketone)
SB  - IM
MH  - Adult
MH  - Amino Acid Chloromethyl Ketones/pharmacology
MH  - Boron Compounds/pharmacology
MH  - Butadienes/pharmacology
MH  - Cells, Cultured
MH  - Chemokine CCL2/*biosynthesis
MH  - Chemokine CXCL1/biosynthesis
MH  - Endometrium/cytology
MH  - Estrenes/pharmacology
MH  - Female
MH  - Humans
MH  - Indoles/pharmacology
MH  - Interleukin-8/*biosynthesis
MH  - Maleimides/pharmacology
MH  - Nitriles/pharmacology
MH  - Pyrrolidinones/pharmacology
MH  - Receptor, PAR-1/antagonists & inhibitors
MH  - Stromal Cells/drug effects/*metabolism
MH  - Thrombin/*pharmacology
EDAT- 2010/12/16 06:00
MHDA- 2011/04/27 06:00
CRDT- 2010/12/16 06:00
PHST- 2010/12/16 06:00 [entrez]
PHST- 2010/12/16 06:00 [pubmed]
PHST- 2011/04/27 06:00 [medline]
AID - deq347 [pii]
AID - 10.1093/humrep/deq347 [doi]
PST - ppublish
SO  - Hum Reprod. 2011 Feb;26(2):407-13. doi: 10.1093/humrep/deq347. Epub 2010 Dec 14.