title: Interleukin-18 augments growth ability of primary human melanocytes by PTEN inactivation through the AKT/NF-κB pathway.
abstract: 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-κB 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.
authors.affiliation: New Drug Screening Center, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Zhou
authors.forename: Jing
authors.initials: J
authors.lastname: Shang
authors.forename: Jing
authors.initials: J
authors.lastname: Song
authors.forename: Fengfeng
authors.initials: F
authors.lastname: Ping
mesh_terms: D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D052816:Foreskin / Q000166:cytology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D020382:Interleukin-18 / Q000494:pharmacology / Q000502:physiology*; D019746:Intramolecular Oxidoreductases / Q000378:metabolism; D008297:Male; D008543:Melanins / Q000096:biosynthesis; D008544:Melanocytes / Q000502:physiology*; D051739:Microphthalmia-Associated Transcription Factor / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D016877:Oxidants / Q000494:pharmacology; D010088:Oxidoreductases / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D010766:Phosphorylation; D061251:Primary Cell Culture; D011499:Protein Processing, Post-Translational; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction
chemical_list: D020382:Interleukin-18; C497234:MITF protein, human; D008543:Melanins; D051739:Microphthalmia-Associated Transcription Factor; D016328:NF-kappa B; D016877:Oxidants; D011994:Recombinant Proteins; D006861:Hydrogen Peroxide; D010088:Oxidoreductases; C064056:tyrosinase-related protein-1; D019009:Proto-Oncogene Proteins c-kit; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase