12-Hydroxyheptadecatrienoic acid promotes epidermal wound healing by accelerating keratinocyte migration via the BLT2 receptor.
Bottom Line: Leukotriene B4 (LTB4) receptor type 2 (BLT2) is a G protein-coupled receptor (GPCR) for 12(S)-hydroxyheptadeca-5Z,8E,10E-trienoic acid (12-HHT) and LTB4.Despite the well-defined proinflammatory roles of BLT1, the in vivo functions of BLT2 remain elusive.These results identify a novel mechanism underlying the action of the 12-HHT/BLT2 axis in epidermal keratinocytes and accordingly suggest the use of BLT2 agonists as therapeutic agents to accelerate wound healing, particularly for intractable wounds, such as diabetic ulcers.
Affiliation: Department of Biochemistry, Juntendo University School of Medicine, Tokyo 113-8421, Japan Department of Medical Biochemistry, Kyushu University, Fukuoka 812-8582, Japan.Show MeSH
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Mentions: To assess the role of the 12-HHT/BLT2 axis in keratinocyte migration during wound repair, an in vitro scratch assay was performed by using mouse and human primary keratinocytes. BLT2 deficiency did not affect primary keratinocyte proliferation (Fig. 5 A). Furthermore, in the absence of 12-HHT (Fig. 5 C, left), the wound closure rate was similar between BLT2 WT and BLT2 KO keratinocytes. However, BLT2 WT keratinocytes exhibited enhanced migration in the presence of 1 nM 12-HHT, whereas BLT2 KO keratinocytes did not (Fig. 5, B and C, right; Videos 1 and 2). This finding was confirmed in normal human epidermal keratinocytes (NHEKs). Both 12-HHT and a synthetic BLT2 agonist, CAY10583 (Iizuka et al., 2005), significantly enhanced NHEK migration relative to control, untreated cells (Fig. 5 D).
Affiliation: Department of Biochemistry, Juntendo University School of Medicine, Tokyo 113-8421, Japan Department of Medical Biochemistry, Kyushu University, Fukuoka 812-8582, Japan.