title: UVB-stimulated TNFα release from human melanocyte and melanoma cells is mediated by p38 MAPK.
abstract: Ultraviolet (UV) radiation activates cell signaling pathways in melanocytes. As a result of altered signaling pathways and UV-induced cellular damage, melanocytes can undergo oncogenesis and develop into melanomas. In this study, we investigated the effect of UV-radiation on p38 MAPK (mitogen-activated protein kinase), JNK and NFκB pathways to determine which plays a major role in stimulating TNFα secretion in human HEM (melanocytes) and MM96L (melanoma) cells. MM96L cells exhibited 3.5-fold higher p38 activity than HEM cells at 5 min following UVA + B radiation and 1.6-fold higher JNK activity at 15-30 min following UVB+A radiation, while NFκB was minimally activated in both cells. Irradiated HEM cells had the greatest fold of TNFα secretion (UVB: 109-fold, UVA + B: 103-fold & UVB+A: 130-fold) when co-exposed to IL1α. The p38 inhibitor, SB202190, inhibited TNFα release by 93% from UVB-irradiated HEM cells. In the UVB-irradiated MM96L cells, both SB202190 and sulfasalazine (NFκB inhibitor) inhibited TNFα release by 52%. Although, anisomycin was a p38 MAPK activator, it inhibited TNFα release in UV-irradiated cells. This suggests that UV-mediated TNFα release may occur via different p38 pathway intermediates compared to those stimulated by anisomycin. As such, further studies into the functional role p38 MAPK plays in regulating TNFα release in UV-irradiated melanocyte-derived cells are warranted.
authors: School of Medical Sciences, RMIT University, PO Box 71, Bundoora VIC 3083, Australia. visalini_muthusamy@rp.edu.sg
authors: Visalini
authors: V
authors: Muthusamy
authors: Terrence J
authors: TJ
authors: Piva
mesh_terms: D000841:Anisomycin / Q000494:pharmacology; D000873:Anthracenes / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000528:radiation effects; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D053582:Interleukin-1alpha / Q000502:physiology; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000528:radiation effects; D008544:Melanocytes / Q000201:enzymology* / Q000378:metabolism / Q000528:radiation effects; D008545:Melanoma; D048055:Mitogen-Activated Protein Kinase 8 / Q000037:antagonists & inhibitors / Q000378:metabolism; D048056:Mitogen-Activated Protein Kinase 9 / Q000037:antagonists & inhibitors / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D011725:Pyridines / Q000494:pharmacology; D012460:Sulfasalazine / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000873:Anthracenes; C508584:IL1A protein, human; D007093:Imidazoles; D053582:Interleukin-1alpha; D016328:NF-kappa B; D011725:Pyridines; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; C432165:pyrazolanthrone; D012460:Sulfasalazine; D000841:Anisomycin; D048056:Mitogen-Activated Protein Kinase 9; D048055:Mitogen-Activated Protein Kinase 8; D048051:p38 Mitogen-Activated Protein Kinases; C090942:4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole
references: Br J Pharmacol. 2010 Jul;160(5):1171-84
references: 20590610
references: Cancer Res. 1999 Mar 15;59(6):1372-7
references: 10096573
references: Arch Dermatol Res. 2010 Jan;302(1):5-17
references: 19756672
references: Clin Exp Metastasis. 2002;19(1):79-85
references: 11918086
references: Mol Cell Biochem. 2008 Jan;308(1-2):193-200
references: 17932622
references: J Biomed Sci. 2007 May;14(3):303-12
references: 17334833
references: Biochem J. 1999 Mar 15;338 ( Pt 3):607-13
references: 10051429
references: Cell Signal. 2008 Feb;20(2):311-22
references: 18068334
references: Mol Cell Biol. 1998 Apr;18(4):1844-54
references: 9528756
references: Biochim Biophys Acta. 2007 Aug;1773(8):1341-8
references: 17306896
references: Curr Opin Cell Biol. 2007 Apr;19(2):142-9
references: 17303404
references: Oncogene. 2013 May 9;32(19):2373-9
references: 22945644
references: J Am Acad Dermatol. 1979 Sep;1(3):249-60
references: 512075
references: Acta Biochim Pol. 2008;55(4):741-8
references: 19023456
references: J Invest Dermatol. 2012 Mar;132(3 Pt 2):896-905
references: 22170491
references: Photodermatol Photoimmunol Photomed. 2009 Feb;25(1):20-9
references: 19152512
references: J Cell Physiol. 1998 Dec;177(3):493-8
references: 9808157
references: Mol Cancer Res. 2003 Feb;1(4):262-70
references: 12612054
references: FASEB J. 2008 Jul;22(7):2379-92
references: 18326785
references: Pigment Cell Melanoma Res. 2008 Aug;21(4):429-38
references: 18541008
references: Pigment Cell Res. 2007 Jun;20(3):216-21
references: 17516929
references: Br J Ophthalmol. 2009 Jan;93(1):91-5
references: 18952645
references: Oncogene. 1999 Jan 21;18(3):813-22
references: 9989833
references: Cell Cycle. 2004 Dec;3(12):1520-3
references: 15611655
references: J Invest Dermatol. 2013 Jan;133(1):221-9
references: 22832488
references: Cancer Res. 2003 Sep 15;63(18):5669-73
references: 14522881
references: Immunol Cell Biol. 2001 Dec;79(6):547-68
references: 11903614
references: Pigment Cell Melanoma Res. 2009 Feb;22(1):66-76
references: 18983537
references: Oxid Med Cell Longev. 2011;2011:728645
references: 21961050
references: Pigment Cell Res. 2001 Dec;14(6):456-65
references: 11775058
references: Clin Dev Immunol. 2009;2009:673952
references: 19434230
references: Photochem Photobiol. 2008 Mar-Apr;84(2):272-83
references: 18353168
references: Apoptosis. 2011 Oct;16(10):1028-41
references: 21786165
references: Pigment Cell Res. 2004 Apr;17(2):173-80
references: 15016307
references: Skin Pharmacol Appl Skin Physiol. 2002 Sep-Oct;15(5):353-9
references: 12239431
references: J Invest Dermatol. 2005 Apr;124(4):857-9
references: 15816846
references: Oncogene. 2001 Apr 26;20(18):2243-53
references: 11402319
references: J Invest Dermatol. 1991 Sep;97(3):405-9
references: 1875041
references: J Invest Dermatol. 2009 Apr;129(4):994-1001
references: 19005488
references: Eur J Immunol. 2007 Mar;37(3):818-29
references: 17301952
references: J Biol Chem. 1999 May 14;274(20):14079-89
references: 10318823
references: Cancer Res. 2001 May 15;61(10):3908-12
references: 11358804
references: Genes Dev. 2004 Sep 15;18(18):2195-224
references: 15371334
references: J Invest Dermatol. 2002 Jun;118(6):1032-7
references: 12060399
references: Pigment Cell Res. 2003 Oct;16(5):434-47
references: 12950718
references: Mol Cancer. 2010 Aug 11;9:214
references: 20701798
references: Cancer Res. 2007 Jan 1;67(1):122-9
references: 17210691
references: Cancer Cell. 2007 May;11(5):447-60
references: 17482134
references: J Invest Dermatol. 1998 May;110(5):806-10
references: 9579550
references: Oncogene. 2004 May 20;23(23):4060-7
references: 15048078
references: Cancer Discov. 2011 Nov;1(6):496-507
references: 22389871
references: Br J Dermatol. 1999 Jun;140(6):995-1009
references: 10354063
references: Pathology. 1979 Apr;11(2):191-5
references: 460945
references: Pigment Cell Melanoma Res. 2010 Jun;23(3):430-40
references: 20337986
references: Cancer. 2009 Jan 1;115(1):128-39
references: 19090007
references: Cell. 2008 Feb 8;132(3):344-62
references: 18267068
references: Clin Cancer Res. 2003 Dec 15;9(17):6419-25
references: 14695143
references: Cancer Res. 1997 Nov 1;57(21):4868-75
references: 9354451
references: Mutat Res. 2004 May 18;549(1-2):65-78
references: 15120963
references: Oncogene. 2000 Jun 15;19(26):3003-12
references: 10871852