Vasoactive intestinal peptide stimulates melanogenesis in B16F10 mouse melanoma cells via CREB/MITF/tyrosinase signaling

• Published in: Biochemical and biophysical research communications 2016-08, Vol.477 (3), p.336-342
• Main Authors: Yuan, Xing-Hua, Yao, Cheng, Oh, Jang-Hee, Park, Chi-Hyun, Tian, Yu-Dan, Han, Mira, Kim, Ji Eun, Chung, Jin Ho, Jin, Zhe-Hu, Lee, Dong Hun
• Format: Article
• Language: English
• Subjects: Animals; B16F10 mouse melanoma cell; CREB; Cyclic AMP Response Element-Binding Protein - metabolism; Melanins - biosynthesis; Melanogenesis; Melanoma, Experimental - metabolism; Melanoma, Experimental - pathology; Mice; Microphthalmia-Associated Transcription Factor - genetics; Microphthalmia-Associated Transcription Factor - metabolism; MITF; Monophenol Monooxygenase - metabolism; RNA, Messenger - genetics; Signal Transduction; Tyrosinase; Vasoactive intestinal peptide; Vasoactive Intestinal Peptide - pharmacology
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2016.06.105

Vasoactive intestinal peptide (VIP), one of the major skin neuropeptides, has been suggested to have active roles in the pathogenesis of inflammatory skin disorders such as atopic dermatitis and psoriasis, which can commonly cause post-inflammatory hyperpigmentation. However, the effect of VIP on melanogenesis remains unknown. In this study, we showed that the melanin contents, tyrosinase activity, and gene expression of tyrosinase and microphthalmia-associated transcription factor (MITF) were significantly increased by treatment with VIP in B16F10 mouse melanoma cells and the stimulatory melanogenic effect was further examined in human epidermal melanocytes (HEMns). In addition, phosphorylated levels of CRE-binding protein (CREB) and protein kinase A (PKA) were markedly increased after VIP treatment, but not p38 mitogen-activated protein kinase (p38 MAPK), extracellular signal-regulated kinase (ERK), or Akt, indicating the possible PKA-CREB signaling pathway involved in VIP-induced melanogenesis. This result was further verified by the fact that VIP induced increased melanin synthesis, and protein levels of phosphorylated CREB, MITF, tyrosinase were significantly attenuated by H89 (a specific PKA inhibitor). These data suggest that VIP-induced upregulation of tyrosinase through the CREB-MITF signaling pathway plays an important role in finding new treatment strategy for skin inflammatory diseases related pigmentation disorders. •Vasoactive intestinal peptide increases melanin production.•Vasoactive intestinal peptide increases tyrosinase activity and gene expression.•Vasoactive intestinal peptide increases MITF both in mRNA and protein levels.•Vasoactive intestinal peptide induces melanogenesis via PKA-CERB signaling pathway.