TY - JOUR
T1 - IL-17 and TNF synergistically modulate cytokine expression while suppressing melanogenesis
T2 - Potential relevance to psoriasis
AU - Wang, Claire Q.F.
AU - Akalu, Yemsratch T.
AU - Suarez-Farinas, Mayte
AU - Gonzalez, Juana
AU - Mitsui, Hiroshi
AU - Lowes, Michelle A.
AU - Orlow, Seth J.
AU - Manga, Prashiela
AU - Krueger, James G.
N1 - Funding Information:
The Milstein Medical Program provided major support for this study. Research was also supported by a Clinical and Translational Science Award grant UL1RR024143 (to JGK), NIH/NIAMS grant AR41880 (to SJO), grant AR060222 (to MAL), and a pilot project grant from New York University School of Medicine (to SJO and PM). We thank Mr Shivaprasad Bhuvanendran and Dr Alison North from the RU Bio-Imaging Resource Center for technical advice, and Dr Kristine E Nograles for technical assistance.
PY - 2013/12
Y1 - 2013/12
N2 - Inflammation-associated pigmentation changes are extremely common, but the etiology underlying this clinical observation remains elusive. Particularly, it is unclear how the myriad of cytokines known to be involved in inflammatory skin processes affect epidermal melanocytes. We sought to determine how IL-17 and tumor necrosis factor (TNF) influence normal human melanocytes, as these two cytokines have been implicated in various skin diseases. IL-17 and TNF jointly stimulated broad inductions of cytokines, including melanoma mitogens CXCL1 and IL-8. Moreover, IL-17 and TNF synergistically inhibited pigmentation-related signaling and melanin production, and induced keratinocyte production of β-defensin 3, an antagonist for melanocortin 1 receptor. When analyzing psoriasis lesions that are known to overexpress IL-17 and TNF, we observed an increase in melanocyte number and a simultaneous decrease in pigmentation signaling. Furthermore, therapeutic neutralization of TNF and IL-17 with mAbs resulted in a rapid recovery of pigment gene expression in psoriasis lesions. These results demonstrate that IL-17 and TNF can affect both the growth and pigment production of melanocytes, which may contribute to the pigmentation changes associated with psoriasis. These findings may allow the development of novel therapeutics for pigmentary disorders and bring new insights into the immune milieu surrounding melanocytes and related neoplasms.
AB - Inflammation-associated pigmentation changes are extremely common, but the etiology underlying this clinical observation remains elusive. Particularly, it is unclear how the myriad of cytokines known to be involved in inflammatory skin processes affect epidermal melanocytes. We sought to determine how IL-17 and tumor necrosis factor (TNF) influence normal human melanocytes, as these two cytokines have been implicated in various skin diseases. IL-17 and TNF jointly stimulated broad inductions of cytokines, including melanoma mitogens CXCL1 and IL-8. Moreover, IL-17 and TNF synergistically inhibited pigmentation-related signaling and melanin production, and induced keratinocyte production of β-defensin 3, an antagonist for melanocortin 1 receptor. When analyzing psoriasis lesions that are known to overexpress IL-17 and TNF, we observed an increase in melanocyte number and a simultaneous decrease in pigmentation signaling. Furthermore, therapeutic neutralization of TNF and IL-17 with mAbs resulted in a rapid recovery of pigment gene expression in psoriasis lesions. These results demonstrate that IL-17 and TNF can affect both the growth and pigment production of melanocytes, which may contribute to the pigmentation changes associated with psoriasis. These findings may allow the development of novel therapeutics for pigmentary disorders and bring new insights into the immune milieu surrounding melanocytes and related neoplasms.
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U2 - 10.1038/jid.2013.237
DO - 10.1038/jid.2013.237
M3 - Article
C2 - 23732752
AN - SCOPUS:84887822783
SN - 0022-202X
VL - 133
SP - 2741
EP - 2752
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 12
ER -