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Terminal Signal: Anti-Inflammatory Effects of α-Melanocyte-Stimulating Hormone Related Peptides Beyond the Pharmacophore

  • Thomas Brzoska
  • Markus Böhm
  • Andreas Lügering
  • Karin Loser
  • Thomas A. Luger
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 681)

Abstract

During the last two decades a significant number of investigations has established the fact that α-Melanocyte-stimulating hormone (α-MSH) is a potent anti-inflammatory mediator. The anti-inflammatory effects of α-MSH can be elicited via melanocortin receptors (MC-Rs) broadly expressed in a number of tissues ranging from the central nervous system to cells of the immune system and on resident somatic cells of peripheral tissues. α-MSH affects various pathways regulating inflammatory responses such as NF-κB activation, expression of adhesion molecules, inflammatory cytokines, chemokine receptors, T-cell proliferation and activity and inflammatory cell migration. In vivo α-MSH has been shown to be anti-inflammatory as well in animal models of fever, irritant and allergic contact dermatitis, cutaneous vasculitis, fibrosis, in ocular, gastrointestinal, brain and allergic airway inflammation and arthritis. A broad range of effects of α-MSH exerted beyond the field of inflammation, its pigmentory capacity being only the most visible aspect, has been one of the major impediments limiting the use of α-MSH in human inflammatory disorders. Interestingly KPV, C-terminal tripeptide of α-MSH, which lacks the entire sequence motif required for binding to any of the known MC-Rs, retains almost all of the anti-inflammatory capacity of the full hormone, but in its activities display a lack of any pigmentory action. While the exact signaling mechanism utilized by KPV and related peptides currently is unknown it has been demonstrated already that significant similarities between anti-inflammatory signaling of α-MSH and those short peptides exist. These α-MSH related tripeptides thus may be useful alternatives for anti-inflammatory peptide therapy. KdPT, a derivative of KPV corresponding to IL-1β193–195, currently is emerging as another tripeptide with potent anti-inflammatory effects. A more limited spectrum of biologic activities, potentially advantageous physicochemical, pharmacokinetic and pharmacodynamic properties as well as the expectation of low costs for pharmaceutical production make these agents interesting candidates for the treatment of immune-mediated inflammatory skin and bowel diseases, allergic asthma and arthritis.

Keywords

Allergic Contact Dermatitis Related Peptide Leukoc Biol Terminal Signal Erythropoietic Protoporphyria 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Landes Bioscience and Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Thomas Brzoska
    • 1
    • 2
  • Markus Böhm
    • 2
  • Andreas Lügering
    • 3
  • Karin Loser
    • 2
  • Thomas A. Luger
    • 2
  1. 1.Dr. Wolff Arzneimittel, GmbHBielefeldGermany
  2. 2.Department of Dermatology and Ludwig Boltzmann Institute for Cell Biology and Immunobiology of the SkinUniversity of MünsterMünsterGermany
  3. 3.Department of Internal MedicineUniversity of MünsterMünsterGermany

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