PMID- 23381627
OWN - NLM
STAT- MEDLINE
DCOM- 20130417
LR  - 20230216
IS  - 1530-0307 (Electronic)
IS  - 0023-6837 (Linking)
VI  - 93
IP  - 3
DP  - 2013 Mar
TI  - Inhibition of p38/Mk2 signaling pathway improves the anti-inflammatory effect of 
      WIN55 on mouse experimental colitis.
PG  - 322-33
LID - 10.1038/labinvest.2012.177 [doi]
AB  - P38/Mk2 (mitogen-activated protein kinase (MAPK)-activated protein kinase-2, also 
      known as MAKAP kinase-2) is a member of the mitogen-activated protein kinases 
      (MAPKs) family, and participates in inflammatory responses directly or 
      indirectly. WIN55, 212-2 (WIN55) is a synthetic non-selective agonist of 
      cannabinoid (CB) receptors with remarkable anti-inflammatory properties. This 
      study was to explore the roles of WIN55 and p38/Mk2 signaling pathway in dextran 
      sodium sulfate (DSS)-induced mouse colitis and ascertain their anti-inflammatory 
      mechanisms. Colitis was induced in C57BL Mk2 gene homozygous deletion (Mk2-/-) 
      and wild-type mice by replacing the drinking water with 4% DSS solution for 7 
      days. DSS-treated mice developed bloody stool, weight loss, and eye-visible 
      multiple bleeding ulcers on colon mucosa. The mRNA expressions levels of TNF-alpha 
      and IL-6, as well as the protein levels of p38 and its phosphorylated form 
      (p-p38), were upregulated in the colon. The plasma levels of TNF-alpha, IL-6, 
      cytokine-induced neutrophil chemoattractant-1 (CINC-1), monocyte chemoattractant 
      protein-1 (MCP-1), and lung myeloperoxidase (MPO) activities were raised; 
      however, all these changes were less severe in Mk2-/- mice. After WIN55 
      intervention, the Mk2-/- mice recovered faster and better from the induced 
      colitis than their wild-type counterparts. The results indicate that the Mk2 
      homozygous deletion in mice impedes the induction of experimental colitis by DSS, 
      confirming the notion that p38/Mk2 is involved in this inflammatory response. 
      WIN55 protects mice against DSS-induced colitis, in particular when the p38/Mk2 
      pathway is obstructed, implying that the activation of CB system, together with 
      blocking of p38/Mk2 pathway, serves as a potential drug target for colitis 
      treatment.
FAU - Li, Yu Y
AU  - Li YY
AD  - Department of Pathophysiology, Institute of Digestive Disease, Tongji University 
      School of Medicine, Shanghai, China. liyongyu@tongji.edu.cn
FAU - Yuece, Birol
AU  - Yuece B
FAU - Cao, Hua M
AU  - Cao HM
FAU - Lin, Hong X
AU  - Lin HX
FAU - Lv, Shuai
AU  - Lv S
FAU - Chen, Jie C
AU  - Chen JC
FAU - Ochs, Stephanie
AU  - Ochs S
FAU - Sibaev, Andrej
AU  - Sibaev A
FAU - Deindl, Elisabeth
AU  - Deindl E
FAU - Schaefer, Claus
AU  - Schaefer C
FAU - Storr, Martin
AU  - Storr M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130204
PL  - United States
TA  - Lab Invest
JT  - Laboratory investigation; a journal of technical methods and pathology
JID - 0376617
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Benzoxazines)
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemokine CXCL1)
RN  - 0 (DNA Primers)
RN  - 0 (Interleukin-6)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Morpholines)
RN  - 0 (Naphthalenes)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 5H31GI9502 
      ((3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone)
RN  - 9042-14-2 (Dextran Sulfate)
RN  - EC 1.11.1.7 (Peroxidase)
RN  - EC 2.7.1.- (MAP-kinase-activated kinase 2)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
SB  - IM
MH  - Analysis of Variance
MH  - Animals
MH  - Anti-Inflammatory Agents/*pharmacology
MH  - Benzoxazines/*pharmacology
MH  - Chemokine CCL2/blood
MH  - Chemokine CXCL1/blood
MH  - Colitis/chemically induced/*drug therapy/pathology
MH  - DNA Primers/genetics
MH  - Dextran Sulfate/toxicity
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Immunohistochemistry
MH  - Interleukin-6/blood
MH  - Intracellular Signaling Peptides and Proteins/deficiency/*genetics/metabolism
MH  - MAP Kinase Signaling System/*drug effects
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Morpholines/*pharmacology
MH  - Naphthalenes/*pharmacology
MH  - Peroxidase/metabolism
MH  - Protein Serine-Threonine Kinases/deficiency/*genetics/metabolism
MH  - Real-Time Polymerase Chain Reaction
MH  - Tumor Necrosis Factor-alpha/blood
EDAT- 2013/02/06 06:00
MHDA- 2013/04/19 06:00
CRDT- 2013/02/06 06:00
PHST- 2013/02/06 06:00 [entrez]
PHST- 2013/02/06 06:00 [pubmed]
PHST- 2013/04/19 06:00 [medline]
AID - S0023-6837(22)00968-0 [pii]
AID - 10.1038/labinvest.2012.177 [doi]
PST - ppublish
SO  - Lab Invest. 2013 Mar;93(3):322-33. doi: 10.1038/labinvest.2012.177. Epub 2013 Feb 
      4.