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
Related in: MedlinePlus
License 1 - License 2
Mentions: Because aspirin treatment inhibits both 12-HHT and TxA2 production (Fig. 1 E), reduced TxA2 levels might also be involved in the deleterious effects of aspirin. To investigate this hypothesis, we performed a punch assay in the dorsal skin of mice lacking TxA2S, the terminal enzyme required for the production of TxA2 and 12-HHT, and mice lacking the TxA2 receptor (TP). TxA2S deficiency delayed wound closure (Fig. 4 A), whereas wound closure was normal in TP KO mice (Fig. 4 B). These findings indicate that a reduction in TxA2 is not responsible for the aspirin-dependent delay in skin wound healing. Wound closure was also normal in mice deficient in BLT1 (Yokomizo et al., 1997), a high-affinity LTB4 receptor (Fig. 4 C), also ruling out the involvement of BLT1 in wound healing. The effect of a COX2 selective inhibitor, celecoxib, on wound healing was also studied. Celecoxib treatment (25 mg/kg body weight) had no effect on wound closure in WT mice (Fig. 4 D). We also measured 12-HHT production in both mouse serum and wound fluid, which was not affected by celecoxib treatment (unpublished data).
Affiliation: Department of Biochemistry, Juntendo University School of Medicine, Tokyo 113-8421, Japan Department of Medical Biochemistry, Kyushu University, Fukuoka 812-8582, Japan.