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Alpha‐Melanocyte‐Stimulating Hormone Modulates Activation of NF‐κB and AP‐1 and Secretion of Interleukin‐8 in Human Dermal Fibroblasts
Author(s) -
BÖHM MARKUS,
SCHULTE URSULA,
KALDEN HENNER,
LUGER T. A.
Publication year - 1999
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1999.tb08685.x
Subject(s) - cytokine , melanocyte stimulating hormone , endocrinology , chemokine , medicine , angiogenesis , chemistry , interleukin , extracellular matrix , fibroblast , hormone , biology , microbiology and biotechnology , receptor , biochemistry , in vitro
Alpha‐melanocyte‐stimulating hormone (α‐MSH) has evolved as a mediator of diverse biological activities in an ever‐growing number of non‐melanocytic cell types. One mechanism by which α‐MSH exerts its effects is modulation of AP‐1 and NF‐κB. These two transcription factors also play an important role in fibroblasts, in extracellular matrix composition, and in cytokine expression. By use of electric mobility shift assays, we demonstrate that α‐MSH (10 −6 to 10 −14 M) activates AP‐1 in human dermal fibroblasts, whereas coincubation with interleukin‐1β (IL‐1β) results in suppression of its activation. α‐MSH also induces activation of NF‐κB but does not modulate DNA binding on costimulation with IL‐1β. Since AP‐1 and NF‐κB are key elements in controlling interleukin‐8 (IL‐8) transcription, human fibroblasts were treated with α‐MSH and IL‐1β for 24 hours, and cytokine levels in the supernatants were measured by ELISA. α‐MSH alone had little effect, whereas coincubation with IL‐1β led to marked downregulation of IL‐8 secretion (at most 288 ± 152 ng/mL) when compared to treatment with IL‐1β alone (919 ± 157 ng/mL). Our results indicate that α‐MSH exerts modulatory effects on the activation of NF‐κB and AP‐1, and that it can regulate chemokine secretion in human dermal fibroblasts. These effects of α‐MSH may have important regulatory functions in extracellular matrix composition, wound healing, or angiogenesis.