PMID- 11230753
OWN - NLM
STAT- MEDLINE
DCOM- 20010412
LR  - 20131121
IS  - 0270-9139 (Print)
IS  - 0270-9139 (Linking)
VI  - 33
IP  - 3
DP  - 2001 Mar
TI  - Agonist-specific regulation of monocyte chemoattractant protein-1 expression by 
      cyclooxygenase metabolites in hepatic stellate cells.
PG  - 713-21
AB  - Activated hepatic stellate cells (HSC) regulate the liver "wound-healing" 
      response through expression of chemokines, including monocyte chemoattractant 
      protein-1 (MCP-1), which participate in the formation of the inflammatory 
      infiltrate during liver injury. Cyclooxygenase (COX) catalyzes the conversion of 
      arachidonic acid into prostaglandins, which may contribute to the inflammatory 
      response. In this study, we investigated the effects of COX inhibitors on the 
      expression of MCP-1 in cultured HSC. Pretreatment of HSC with nonspecific COX 
      inhibitors such as indomethacin or ibuprofen markedly reduced the expression of 
      MCP-1 caused by exposure to tumor necrosis factor alpha (TNF-alpha) or 
      interleukin-1alpha (IL-1alpha). NS-398, a specific COX-2 inhibitor, also resulted 
      in a dose-dependent inhibition of MCP-1 gene and protein expression. These 
      effects were dependent on reduced MCP-1 transcription, as established using a 
      reporter plasmid. In contrast, the up-regulation of MCP-1 expression caused by 
      interferon gamma (IFN-gamma) was not sensitive to COX inhibitors. Quiescent HSC 
      did not show detectable expression of COX-2, which became evident after 
      activation in culture, and while TNF-alpha and IL-1alpha markedly increased the 
      expression of COX-2, IFN-gamma did not have any effects. Pretreatment of HSC with 
      the stable cyclic adenosine monophosphate (cAMP) analog, 8-bromo cAMP, reverted 
      the effects of the COX-2 inhibitor, but not of a nuclear factor-kappaB 
      (NF-kappaB) inhibitor, demonstrating that prostaglandins modulate MCP-1 
      expression via production of cAMP. On the other hand, the action of NF-kappaB 
      inhibitors was negligible in IFN-gamma-stimulated cells. These findings indicate 
      that cross-talk between cytokines and a prostaglandin-cAMP pathway differentially 
      regulates the proinflammatory potential of HSC, contributing to the modulation of 
      liver tissue inflammation.
FAU - Efsen, E
AU  - Efsen E
AD  - Dipartimento di Medicina Interna, University of Florence, Italy.
FAU - Bonacchi, A
AU  - Bonacchi A
FAU - Pastacaldi, S
AU  - Pastacaldi S
FAU - Valente, A J
AU  - Valente AJ
FAU - Wenzel, U O
AU  - Wenzel UO
FAU - Tosti-Guerra, C
AU  - Tosti-Guerra C
FAU - Pinzani, M
AU  - Pinzani M
FAU - Laffi, G
AU  - Laffi G
FAU - Abboud, H E
AU  - Abboud HE
FAU - Gentilini, P
AU  - Gentilini P
FAU - Marra, F
AU  - Marra F
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Hepatology
JT  - Hepatology (Baltimore, Md.)
JID - 8302946
RN  - 0 (Chemokine CCL2)
RN  - 0 (Cyclooxygenase 2 Inhibitors)
RN  - 0 (Cyclooxygenase Inhibitors)
RN  - 0 (Interleukin-1)
RN  - 0 (Isoenzymes)
RN  - 0 (Membrane Proteins)
RN  - 0 (NF-kappa B)
RN  - 0 (Nitrobenzenes)
RN  - 0 (Sulfonamides)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 123653-11-2 (N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide)
RN  - 23583-48-4 (8-Bromo Cyclic Adenosine Monophosphate)
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - EC 1.14.99.1 (PTGS2 protein, human)
RN  - EC 1.14.99.1 (Prostaglandin-Endoperoxide Synthases)
RN  - WK2XYI10QM (Ibuprofen)
RN  - XXE1CET956 (Indomethacin)
SB  - IM
MH  - 8-Bromo Cyclic Adenosine Monophosphate/pharmacology
MH  - Cells, Cultured
MH  - Chemokine CCL2/*agonists/genetics/*metabolism
MH  - Cyclic AMP/physiology
MH  - Cyclooxygenase 2
MH  - Cyclooxygenase 2 Inhibitors
MH  - Cyclooxygenase Inhibitors/pharmacology
MH  - Gene Expression/drug effects
MH  - Humans
MH  - Ibuprofen/pharmacology
MH  - Indomethacin/pharmacology
MH  - Interleukin-1/pharmacology
MH  - Isoenzymes/antagonists & inhibitors/metabolism
MH  - Liver/cytology/drug effects/*metabolism
MH  - Membrane Proteins
MH  - NF-kappa B/physiology
MH  - Nitrobenzenes/pharmacology
MH  - Prostaglandin-Endoperoxide Synthases/*metabolism
MH  - Sulfonamides/pharmacology
MH  - Transcription, Genetic/drug effects
MH  - Tumor Necrosis Factor-alpha/pharmacology
EDAT- 2001/03/07 10:00
MHDA- 2001/04/17 10:01
CRDT- 2001/03/07 10:00
PHST- 2001/03/07 10:00 [pubmed]
PHST- 2001/04/17 10:01 [medline]
PHST- 2001/03/07 10:00 [entrez]
AID - S0270-9139(01)00509-2 [pii]
AID - 10.1053/jhep.2001.22761 [doi]
PST - ppublish
SO  - Hepatology. 2001 Mar;33(3):713-21. doi: 10.1053/jhep.2001.22761.