Document Detail


Protective role of the leukotriene B4 receptor BLT2 in murine inflammatory colitis.
MedLine Citation:
PMID:  20667973     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BLT2 is a low-affinity leukotriene B(4) (LTB(4)) receptor that is activated by 12(S)-hydroxyheptadeca-5Z,8E,10E-trienoic acid (12-HHT) and LTB(4). Despite the well-defined proinflammatory roles of BLT1, the in vivo functions of BLT2 remain elusive. To clarify the role of BLT receptors in intestinal inflammation, we assessed susceptibility to dextran sodium sulfate (DSS)-induced colitis in mice lacking either BLT1 or BLT2. BLT2(-/-) mice exhibited increased sensitivity to DSS as compared to wild-type and BLT1(-/-) mice, with more severe body weight loss and inflammation. Expression of inflammatory cytokines such as interferon (IFN)-γ, interleukin (IL)-1β, and IL-6, chemokines such as CXC chemokine ligand 9 (CXCL9) and C-C motif chemokine 19 (CCL19), and metalloproteinases was highly up-regulated in the colons of DSS-treated BLT2(-/-) mice, and there was an enhanced accumulation of activated macrophages. Phosphorylation of the signal transducer and activator of transcription 3 (STAT3) was also markedly accelerated in the crypts of DSS-treated BLT2(-/-) mice. Madin-Darby canine kidney II (MDCKII) cells transfected with BLT2 exhibited enhanced barrier function as measured by transepithelial electrical resistance (TER) and FITC-dextran leakage through MDCK monolayers. Thus, BLT2 is expressed in colon cryptic cells and appears to protect against DSS-induced colitis, possibly by enhancing barrier function in epithelial cells of the colon. These novel results suggest a direct anti-inflammatory role of BLT2 that is distinct from the proinflammatory roles of BLT1.
Authors:
Yoshiko Iizuka; Toshiaki Okuno; Kazuko Saeki; Hiroshi Uozaki; Shinji Okada; Takumi Misaka; Tetsuya Sato; Hiroyuki Toh; Masashi Fukayama; Naoki Takeda; Yoshihiro Kita; Takao Shimizu; Motonao Nakamura; Takehiko Yokomizo
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-07-28
Journal Detail:
Title:  FASEB journal : official publication of the Federation of American Societies for Experimental Biology     Volume:  24     ISSN:  1530-6860     ISO Abbreviation:  FASEB J.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-12-02     Completed Date:  2011-01-04     Revised Date:  2012-02-15    
Medline Journal Info:
Nlm Unique ID:  8804484     Medline TA:  FASEB J     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4678-90     Citation Subset:  IM    
Affiliation:
Department of Medical Biochemistry, Graduate School of Medical Sciences, The University of Tokyo, Tokyo, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Line
Cells, Cultured
Colitis / chemically induced,  genetics*,  metabolism
Colon / metabolism
Cytokines / metabolism
Dextran Sulfate / toxicity
Dogs
Female
Immunoblotting
Immunohistochemistry
Inflammation / immunology,  metabolism*
Interferon-gamma / metabolism
Interleukin-1beta / metabolism
Interleukin-6 / metabolism
Intestinal Mucosa / metabolism
Macrophages / immunology,  metabolism
Male
Mice
Mice, Mutant Strains
Oligonucleotide Array Sequence Analysis
Receptors, Leukotriene B4 / genetics,  metabolism*
Reverse Transcriptase Polymerase Chain Reaction
Chemical
Reg. No./Substance:
0/Cytokines; 0/Interleukin-1beta; 0/Interleukin-6; 0/Ltb4r1 protein, mouse; 0/Ltb4r2 protein, mouse; 0/Receptors, Leukotriene B4; 82115-62-6/Interferon-gamma; 9042-14-2/Dextran Sulfate

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