title: Enhancement of the p38 MAPK and PKA signaling pathways is associated with the pro-melanogenic activity of Interleukin 33 in primary melanocytes.
abstract: BACKGROUND
  Interleukin-33 (IL-33) was recently recognized as a member of the IL-1 cytokine family. The triggers no matter environmental or endogenous that provoke IL-33 cellular release may be associated with inflammation, infection or tissue damage. However, to date, the regulatory role of IL-33 in the control of melanogenesis has not been elucidated.
  
  
  OBJECTIVE
  The present study was designed to investigate the effect of IL-33 on melanogenesis and to explore its underlying mechanisms.
  
  
  METHODS
  Melanocytes were exposed to IL-33. Then cell viabilities were measured by MTT assay. The improving activities of IL-33 were examined by melanin synthesis, tyrosinase (TYR) activity assay. The expressions of relative proteins were assessed by Western blotting.
  
  
  RESULTS
  IL-33 increased the TYR activity and melanin content in a dosage-dependent manner at concentrations of 1-10ng/ml. Treatment with 10ng/ml of IL-33 enhanced the expression of microphthalmia-associated transcription factor (MITF), TYR, tyrosinase-related protein 1 (TRP-1) and dopachrome tautomerase (DCT) in normal human foreskin-derived epidermal melanocytes (NHEM). Furthermore, IL-33 could remarkably promote the phosphorylation levels of p38 mitogen-activated protein kinases (MAPKs) and cyclic AMP-responsive element-binding protein (CREB). This pro-melanogenic effect could be partially reversed by the pre-treatment with the special p38 MAPK inhibitor, SB203580, and protein kinase A (PKA) inhibitor, H89.
  
  
  CONCLUSIONS
  Our results collectively indicated that IL-33 improved melanin biosynthesis in NHEM. This function might be attributed to the fact that IL-33 stimulates the phosphorylation of p38 MAPK and CREB, increases the TYR, TRP-1 and DCT expression through MITF, finally resulting in the augment of melanogenesis.
authors.affiliation: Center for Drug Screening, China Pharmaceutical University, Nanjing 210009, China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Center for Drug Screening, China Pharmaceutical University, Nanjing 210009, China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Song
authors.affiliation: Center for Drug Screening, China Pharmaceutical University, Nanjing 210009, China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, China.
authors.forename: Fengfeng
authors.initials: F
authors.lastname: Ping
authors.affiliation: Center for Drug Screening, China Pharmaceutical University, Nanjing 210009, China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, China. Electronic address: shangjing21cn@163.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Shang
mesh_terms: D000293:Adolescent; D002470:Cell Survival; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007093:Imidazoles / Q000737:chemistry; D007375:Interleukin-1 / Q000378:metabolism; D000067596:Interleukin-33; D007378:Interleukins / Q000494:pharmacology*; D007546:Isoquinolines / Q000737:chemistry; D008297:Male; D008544:Melanocytes / Q000166:cytology*; D014442:Monophenol Monooxygenase / Q000378:metabolism; D010766:Phosphorylation; D010858:Pigmentation; D011725:Pyridines / Q000737:chemistry; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction; D013449:Sulfonamides / Q000737:chemistry; D055815:Young Adult; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D016207:Cytokines; C506536:IL33 protein, human; D007093:Imidazoles; D007375:Interleukin-1; D000067596:Interleukin-33; D007378:Interleukins; D007546:Isoquinolines; D011725:Pyridines; D011994:Recombinant Proteins; D013449:Sulfonamides; D014442:Monophenol Monooxygenase; D017868:Cyclic AMP-Dependent Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; C093642:SB 203580
keywords: CREB; IL-33; Melanogenesis; NHEM; PKA; p38 MAPK