Tsuruki Takahiro, Takahata Kyoya, Yoshikawa Masaaki
Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, Japan.
Biosci Biotechnol Biochem. 2007 May;71(5):1198-202. doi: 10.1271/bbb.60656. Epub 2007 May 7.
Previously, we found that an intraperitoneally administered chemotactic peptide, N-formyl-Met-Leu-Phe (fMLP), and MMK-1, a selective agonist of formyl peptide receptor-like 1 (FPRL1) receptor, the low affinity subtype of the fMLP receptor, prevented the alopecia in neonatal rats induced by the anticancer agent etoposide. The anti-alopecia effect of fMLP was not inhibited at all by Boc-FLFLF, a selective antagonist of formylpeptide receptor (FPR), which is the high affinity subtype of the fMLP receptor, but it was partly inhibited by Trp-Arg-Trp-Trp-Trp-Trp-NH(2) (WRW(4)), an antagonist of FPRL1 receptor. On the other hand, the anti-alopecia effect of MMK-1 was completely abolished by WRW(4). The anti-alopecia effects of fMLP and MMK-1 were also inhibited by Lys-D-Pro-Thr (K(D)PT) and pyrrolidine dithiocarbamate, which are inhibitors of interleukin-1 (IL-1) and nuclear factor-kappaB (NF-kappaB) respectively. Hence, we suggest that the anti-alopecia mechanisms of intraperitoneally administered fMLP and MMK-1 include activation of NF-kappaB via IL-1 release downstream of the FPRL1 receptor homolog in rats.
此前，我们发现腹腔注射趋化肽N-甲酰甲硫氨酰-亮氨酰-苯丙氨酸（fMLP）以及MMK-1（甲酰肽受体样1（FPRL1）受体的选择性激动剂，fMLP受体的低亲和力亚型）可预防抗癌药依托泊苷诱导的新生大鼠脱发。fMLP的抗脱发作用完全不受fMLP受体高亲和力亚型甲酰肽受体（FPR）的选择性拮抗剂Boc-FLFLF的抑制，但部分受到FPRL1受体拮抗剂Trp-Arg-Trp-Trp-Trp-Trp-NH₂（WRW₄）的抑制。另一方面，MMK-1的抗脱发作用被WRW₄完全消除。fMLP和MMK-1的抗脱发作用也分别受到白细胞介素-1（IL-1）抑制剂Lys-D-Pro-Thr（KDPT）和核因子-κB（NF-κB）抑制剂吡咯烷二硫代氨基甲酸盐的抑制。因此，我们认为腹腔注射fMLP和MMK-1的抗脱发机制包括通过大鼠FPRL1受体同源物下游的IL-1释放激活NF-κB。
