PMID- 19818401
OWN - NLM
STAT- MEDLINE
DCOM- 20100216
LR  - 20211122
IS  - 0006-3002 (Print)
IS  - 0006-3002 (Linking)
VI  - 1792
IP  - 12
DP  - 2009 Dec
TI  - Mechanisms of dexamethasone-mediated chemokine down-regulation in mild and severe 
      acute pancreatitis.
PG  - 1205-11
LID - 10.1016/j.bbadis.2009.10.001 [doi]
AB  - This study aimed to investigate the role of therapeutic dexamethasone (Dex) 
      treatment on the mechanisms underlying chemokine expression during mild and 
      severe acute pancreatitis (AP) experimentally induced in rats. Regardless of the 
      AP severity, Dex (1 mg/kg), administered 1 h after AP, reduced the acinar cell 
      activation of extracellular signal-regulated kinase (ERK) and 
      c-Jun-NH(2)-terminal kinase (JNK) but failed to reduce p38-mitogen-activated 
      protein kinase (MAPK) in severe AP. In both AP models, Dex inhibited the 
      activation of nuclear factor-kappaB (NF-kappaB) and signal transducers and 
      activators of transcription (STAT) factors. All of this resulted in pancreatic 
      down-regulation of the chemokines monocyte chemoattractant protein-1 (MCP-1) and 
      cytokine-induced neutrophil chemoattractant (CINC). Lower plasma chemokine levels 
      as well as decreased amylasemia, hematocrit and plasma interleukin-1beta 
      (Il-1beta) levels were found either in mild or severe AP treated with Dex. 
      Pancreatic neutrophil infiltration was attenuated by Dex in mild but not in 
      severe AP. In conclusion, by targeting MAPKs, NF-kappaB and STAT3 pathways, Dex 
      treatment down-regulated the chemokine expression in different cell sources 
      during mild and severe AP, resulting in decreased severity of the disease.
FAU - Yubero, S
AU  - Yubero S
AD  - Department of Physiology and Pharmacology, University of Salamanca, 37007 
      Salamanca, Spain.
FAU - Ramudo, L
AU  - Ramudo L
FAU - Manso, M A
AU  - Manso MA
FAU - De Dios, I
AU  - De Dios I
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20091007
PL  - Netherlands
TA  - Biochim Biophys Acta
JT  - Biochimica et biophysica acta
JID - 0217513
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemokine CXCL1)
RN  - 0 (Cxcl1 protein, rat)
RN  - 0 (NF-kappa B)
RN  - 0 (RNA, Messenger)
RN  - 0 (STAT3 Transcription Factor)
RN  - 7S5I7G3JQL (Dexamethasone)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Acute Disease
MH  - Animals
MH  - Anti-Inflammatory Agents/*pharmacology
MH  - Blotting, Western
MH  - Cell Nucleus/metabolism
MH  - Chemokine CCL2/genetics/*metabolism
MH  - Chemokine CXCL1/genetics/*metabolism
MH  - Dexamethasone/*pharmacology
MH  - Down-Regulation
MH  - Male
MH  - Mitogen-Activated Protein Kinases/genetics/metabolism
MH  - NF-kappa B/genetics/metabolism
MH  - Pancreatitis/*drug therapy/*metabolism/pathology
MH  - RNA, Messenger/genetics/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - STAT3 Transcription Factor/genetics/metabolism
EDAT- 2009/10/13 06:00
MHDA- 2010/02/17 06:00
CRDT- 2009/10/13 06:00
PHST- 2009/09/02 00:00 [received]
PHST- 2009/09/28 00:00 [revised]
PHST- 2009/10/01 00:00 [accepted]
PHST- 2009/10/13 06:00 [entrez]
PHST- 2009/10/13 06:00 [pubmed]
PHST- 2010/02/17 06:00 [medline]
AID - S0925-4439(09)00225-7 [pii]
AID - 10.1016/j.bbadis.2009.10.001 [doi]
PST - ppublish
SO  - Biochim Biophys Acta. 2009 Dec;1792(12):1205-11. doi: 
      10.1016/j.bbadis.2009.10.001. Epub 2009 Oct 7.