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Truncated peptide derivates of the C‐terminal domain of alpha‐MSH (11–13) – emerging agents for anti‐inflammatory future therapy
Author(s) -
Böhm M.,
Mastrofrancesco A.,
Stroszek E.,
Kokot A.,
Zouboulis C. C.,
Luger T. A.
Publication year - 2008
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/j.1600-0625.2008.00742_13.x
Subject(s) - proinflammatory cytokine , peptide , pharmacophore , tripeptide , chemistry , in vitro , biology , biochemistry , microbiology and biotechnology , inflammation , immunology
There is increasing evidence that selected peptide fragments of the neuropeptide alpha‐melanocyte‐stimulating hormone (alpha‐MSH) have preserved immunomodulatory effects in various in vitro and in vivo models. However, until recently, emphasis has been attributed mostly to peptides related to the central pharmacophore of alpha‐MSH (6–9) as well as to peptides homologous to the C‐terminal tripeptide sequence, MSH (11–13). Here we investigated in detail the in vitro effects of an alpha MSH (11–13) derivative, K(D)PT, in which the last amino acid valine of alpha‐MSH (11–13) was substituted by threonine and by the D‐enantiomer of proline in position 2. Using the immortalized human sebocyte cell line SZ95 as an in vitro model we demonstrate that K(D)PDT has potent antagonistic effects against interleukin (IL)‐induced activation of NF‐kB presumably by inhibiting IkBalpha protein degradation. In contrast IL‐1‐mediated activation of the stress kinase p38 was not affected. The significance of the NF‐kB‐modulatory effect of K(D)PT was highlighted by suppression of IL‐1‐mediated mRNA expression and protein secretion of IL‐6 and IL‐8, two proinflammatory cytokines crucially implicated in the pathogenesis of acne vulgaris. Interestingly, K(D)PT likewise suppressed P. acnes‐induced expression of IL‐6 and IL‐8. Our in vitro data are promising towards the therapeutic exploitation of small peptide derivatives of the C‐terminal domain of alpha‐MSH, e.g. K(D)PT, not only for the treatment of acne but also for many other inflammatory skin diseases.