Premium
Roles of 12‐HHT/LTB4 receptor, BLT2 in murine inflammatory colitis
Author(s) -
Okuno Toshiaki,
Iizuka Yoshiko,
Saeki Kazuko,
Yokomizo Takehiko
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.551.9
BLT2 is originally identified as a low‐affinity leukotriene B4 (LTB4) receptor, and recently we found that 12(S)‐hydroxyheptadeca‐5Z, 8E, 10E‐trienoic acid (12‐HHT) is a high‐affinity ligand for BLT2. Despite the well‐defined pro‐inflammatory roles of BLT1, the in vivo functions of BLT2 remain elusive. To clarify the role of BLT2 in intestinal inflammation, we assessed susceptibility to dextran sodium sulfate (DSS)‐induced colitis in mice lacking BLT2. BLT2 −/− mice exhibited increased sensitivity to DSS as compared to WT, with more severe body weight loss and inflammation. Expression of inflammatory cytokines such as IFNγ, IL‐1β, and IL‐6, chemokines such as CXCL9 and CCL19, and metalloproteinases was highly upregulated in the colons of DSS‐treated BLT2 −/− mice, and there was an enhanced accumulation of activated macrophages. Phosphorylation of Stat3 was also markedly accelerated in the crypts of DSS‐treated BLT2 −/− mice. 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 pro‐inflammatory roles of BLT1.