PMID- 23178856 OWN - NLM STAT- MEDLINE DCOM- 20130705 LR - 20161125 IS - 1878-5875 (Electronic) IS - 1357-2725 (Linking) VI - 45 IP - 2 DP - 2013 Feb TI - Interleukin-18 augments growth ability of primary human melanocytes by PTEN inactivation through the AKT/NF-kappaB pathway. PG - 308-16 LID - S1357-2725(12)00371-8 [pii] LID - 10.1016/j.biocel.2012.11.008 [doi] AB - Normal human skin relies on melanocytes to provide photoprotection and thermoregulation by producing melanin. The growth and behavior of melanocytes are controlled by many factors. Interleukin-18 (IL-18) is expressed in both immune and non-immune cells and participates in the adjustment of multitude cellular functions. Nonetheless, the regulative roles of IL-18 in melanogenesis and growth of melanocytes have not been explored. The present study was conducted to investigate the effects of IL-18 on melanocytes and elucidate the underlying mechanisms. We proved that IL-18 increased the tyrosinase activity and melanin content in normal human foreskin-derived epidermal melanocytes (NHEM). Treatment with IL-18 (20 ng/ml) enhanced the expression of c-Kit, microphtalmia-associated transcription factor (MITF) and its downstream tyrosinase-related protein 1 (TRP-1), and TRP-2. In addition, IL-18 induced NHEM migration at concentration of 20 ng/ml. These results indicated a promotive action of IL-18 on melanogenesis in NHEM. Our data revealed that IL-18 stimulated ERK1/2 and NF-kappaB activation, improved p-Akt, p70 S6K and anti-apoptotic Bcl-2 levels, and deactivated phosphatase and tensin homolog deleted on chromosome 10 (PTEN) in NHEM. Besides, IL-18 increased level of PTEN phosphorylation to protect NHEM from damage induced by H(2)O(2). These results in vitro showed the accommodation of IL-18 in melanocytes growth. Therefore, we suggested an important regulating action of IL-18 to melanogenesis and cell growth ability of skin melanocytes. CI - Copyright (c) 2012 Elsevier Ltd. All rights reserved. FAU - Zhou, Jia AU - Zhou J AD - New Drug Screening Center, China Pharmaceutical University, Nanjing 210009, China. FAU - Shang, Jing AU - Shang J FAU - Song, Jing AU - Song J FAU - Ping, Fengfeng AU - Ping F LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20121122 PL - Netherlands TA - Int J Biochem Cell Biol JT - The international journal of biochemistry & cell biology JID - 9508482 RN - 0 (Interleukin-18) RN - 0 (MITF protein, human) RN - 0 (Melanins) RN - 0 (Microphthalmia-Associated Transcription Factor) RN - 0 (NF-kappa B) RN - 0 (Oxidants) RN - 0 (Recombinant Proteins) RN - BBX060AN9V (Hydrogen Peroxide) RN - EC 1.- (Oxidoreductases) RN - EC 1.14.18.- (tyrosinase-related protein-1) RN - EC 2.7.10.1 (Proto-Oncogene Proteins c-kit) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases) RN - EC 3.1.3.67 (PTEN Phosphohydrolase) RN - EC 3.1.3.67 (PTEN protein, human) RN - EC 5.3.- (Intramolecular Oxidoreductases) RN - EC 5.3.3.12 (dopachrome isomerase) SB - IM MH - Cell Movement MH - *Cell Proliferation MH - Cell Survival MH - Cells, Cultured MH - Extracellular Signal-Regulated MAP Kinases/metabolism MH - Foreskin/cytology MH - Humans MH - Hydrogen Peroxide/pharmacology MH - Interleukin-18/pharmacology/*physiology MH - Intramolecular Oxidoreductases/metabolism MH - Male MH - Melanins/biosynthesis MH - Melanocytes/*physiology MH - Microphthalmia-Associated Transcription Factor/metabolism MH - NF-kappa B/metabolism MH - Oxidants/pharmacology MH - Oxidoreductases/metabolism MH - PTEN Phosphohydrolase/*metabolism MH - Phosphorylation MH - Primary Cell Culture MH - Protein Processing, Post-Translational MH - Proto-Oncogene Proteins c-akt/metabolism MH - Proto-Oncogene Proteins c-kit/metabolism MH - Recombinant Proteins/pharmacology MH - *Signal Transduction EDAT- 2012/11/28 06:00 MHDA- 2013/07/06 06:00 CRDT- 2012/11/27 06:00 PHST- 2012/09/09 00:00 [received] PHST- 2012/11/08 00:00 [revised] PHST- 2012/11/12 00:00 [accepted] PHST- 2012/11/27 06:00 [entrez] PHST- 2012/11/28 06:00 [pubmed] PHST- 2013/07/06 06:00 [medline] AID - S1357-2725(12)00371-8 [pii] AID - 10.1016/j.biocel.2012.11.008 [doi] PST - ppublish SO - Int J Biochem Cell Biol. 2013 Feb;45(2):308-16. doi: 10.1016/j.biocel.2012.11.008. Epub 2012 Nov 22.