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Mechanisms of Antiinflammatory Action of α‐MSH Peptides: In Vivo and in Vitro Evidence

LIPTON J. M., ZHAO H., ICHIYAMA T. +2 more1999Annals of the New York Academy of SciencesReview
10.1111/j.1749-6632.1999.tb08674.xPubMed
CardiovascularEndocrine (ADH/ACTH/MSH)GastrointestinalHypothalamic-PituitaryImmune/InnateMusculoskeletalNeurologicalOcularRespiratory/Sinus
ActinomycetesBacterial EndotoxinsIndoor Mold (Stachybotrys, Aspergillus, etc.)MycotoxinsVolatile Organic Compounds (VOCs)Water-Damaged Buildings (WDB)

Abstract

ABSTRACT: α‐Melanocyte stimulating hormone (α‐MSH) modulates all forms of inflammation by acting on peripheral inflammatory cells, glial inflammatory cells, and on CNS receptors that activate descending antiinflammatory neural pathways. The multiple actions of this ancient peptide suggest that there is no singular biochemical mechanism through which it exerts its antiinflammatory activity. However, research on IL‐10 deficient and Agouti protein hypersecreting mice provide new insights into the actions of the peptide in living animals. Studies of cultured human astrocytes, whole murine brain, and human monocyte/macrophages indicate that a primary effect of the peptide is modulation of activation of the nuclear transcription factor κB. The latter influence may underlie the established reduction of gene expression and production of proinflammatory peptides and inducible nitric oxide by α‐MSH peptides.

Key Biomarkers

Alpha Melanocyte Stimulating Hormone (MSH)Immunoglobulin E (IgE)LeptinMatrix Metalloproteinase 9 (MMP9)Vascular Endothelial Growth Factor (VEGF)Visual Contrast Sensitivity (VCS)

Symptom Clusters

Chronic painFatigueHeadacheLight sensitivityMetabolic symptoms (excessive thirst, frequent urination)Mood and appetite swingsMuscle and joint painNeurological symptoms (memory loss, concentration difficulty, confusion, word-finding difficulty)Respiratory symptoms (cough, shortness of breath)Sinus congestionSleep disturbance (night sweats)Tingling in extremities

Cited By (7)

  • Targeting melanocortin receptors as a novel strategy to control inflammationPharmacological Reviews · 2004
  • Sick building syndrome (SBS) and exposure to water-damaged buildings: Time series study, clinical trial and mechanismsNeurotoxicology and Teratology · 2006
  • α-Melanocyte-Stimulating Hormone Inhibits Allergic Airway InflammationThe Journal of Immunology · 2003
  • α-Melanocyte-stimulating Hormone Inhibits Lipopolysaccharide-induced Tumor Necrosis Factor-α Production in Leukocytes by Modulating Protein Kinase A, p38 Kinase, and Nuclear Factor κB Signaling PathwaysJournal of Biological Chemistry · 2003
  • Lipopolysaccharide-induced leptin synthesis and release are differentially controlled by alpha-melanocyte-stimulating hormoneNeuroImmunoModulation · 2005
  • Effect of Alpha-Melanocyte-Stimulating Hormone on Interleukin 8 and Monocyte Chemotactic Protein 1 Expression in a Human Retinal Pigment Epithelial Cell LineOphthalmic Research · 2005

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References (4)

  • Anti-inflammatory actions of the neuroimmunomodulator α-MSHImmunology Today · 1997
  • Targeted disruption of the melanocortin-4 receptor results in obesity in miceCell · 1997
  • Receptor biology of the melanocortins, a family of neuroimmunomodulatory peptidesNeuroImmunoModulation · 1996
  • Alpha- Melanocyte-stimulating hormone induces hapten-specific tolerance in miceThe Journal of Immunology · 1996
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