Proopiomelanocortin-derived Peptides Are Synthesized
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چکیده
Proopiomelanocortin (POMC), the precursor for melanotropic, corticotropic, and opioid peptides such as a-melanocytestimulating hormone (aMSH), ACTH, and other related peptides, was originally identified as a product of the pituitary gland. However, recent evidence shows that POMC products can also be produced by nonpituitary tissues. Because keratinocytes, the major constituent of the epidermis exhibit the capacity to release a variety of proinflammatory and immunomodulatory mediators, the present study was performed to investigate whether human keratinocytes are able to produce POMC-derived peptides. Supernatants of human normal keratinocytes and an epidermal carcinoma cell line (A431 ) contained significant levels of immunoreactive aMSH and ACIH. Upon immuneprecipitation and size-exclusion chromatography, keratinocyte-derived aMSH exhibited a molecular mass of 1 kD and was biologically active as demonstrated in a tyrosinase bioassay. Northern blot analysis revealed the expression of POMC-specific transcripts (1.3 kb) in both normal keratinocytes and A431 cells. The production of aMSH and ACTH could be significantly upregulated both at the protein and mRNA level upon treatment with phorbol myristate acetate, ultraviolet light, or interleukin 1. These data provide first evidence that human keratinocytes produce POMC-derived peptides such as aMSH and ACTH. Because POMC-derived peptides recently have been recognized as potent immunomodulatory mediators, their presence in the epidermis may have a major impact on the skin immune system. (J. Clin. Invest. 1994. 93:2258-2262.)
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تاریخ انتشار 2013