Identification of alpha-melanocyte stimulating hormone as a potential immunosuppressive factor in aqueous humor
Abstract
The aqueous humor of the eye contains factors that regulate immunological responses within the immunosuppressive ocular microenvironment. Besides TGF-beta, the proteins in the low molecular weight (< 3500 Da) fraction of normal aqueous humor are also immunosuppressive. The low molecular weight fraction of aqueous humor inhibits IFN-gamma production and proliferation of antigen-stimulated lymph node cells. Neuropeptides are one possible family of low molecular weight factors in aqueous humor. Through the utilization of an antigen capturing enzyme-assay, the immunosuppressive neuropeptide alpha-melanocyte stimulating hormone (alpha-MSH) was detected in normal aqueous humor of humans, rabbits, and mice. The mean concentration of alpha-MSH in normal aqueous humor of humans was 20 +/- 3 pM, of rabbits 11 +/- 1 pM, of BALB/c mice 16 +/- 3 pM, and of C57BL/6 mice 14 +/- 3 pM. These physiological concentrations of alpha-MSH inhibited the production of IFN-gamma by antigen-stimulated lymph node cells. In contrast to the low molecular weight fraction, alpha-MSH did not inhibit proliferation. There was a 26% recovery of IFN-gamma production when alpha-MSH was absorbed from the low molecular weight fraction. The results demonstrate neuropeptides to be constitutive components of normal aqueous humor and that factors with the capability of differential regulation of effector T-cell activity may be present within the immunosuppressive ocular microenvironment.
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Cited By (39)
- Anti-inflammatory actions of the neuroimmunomodulator α-MSHImmunology Today · 1997
- α-Melanocyte-Stimulating Hormone and Related Tripeptides: Biochemistry, Antiinflammatory and Protective Effects in Vitro and in Vivo, and Future Perspectives for the Treatment of Immune-Mediated Inflammatory DiseasesEndocrine Reviews
- The immunomodulating neuropeptide alpha-melanocyte-stimulating hormone (α-MSH) suppresses LPS-stimulated TLR4 with IRAK-M in macrophagesJournal of Neuroimmunology · 2005
- In vitro induction of CD25+ CD4+ regulatory T cells by the neuropeptide alpha‐melanocyte stimulating hormone (α‐MSH)Immunology and Cell Biology · 2001
- Sick building syndrome (SBS) and exposure to water-damaged buildings: Time series study, clinical trial and mechanismsNeurotoxicology and Teratology · 2006
- Mechanisms of Antiinflammatory Action of the Neuroimmunomodulatory Peptide α‐MSHAnnals of the New York Academy of Sciences · 1998
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