Abstract
There is an important role for α-MSH and the melanocortin receptors in ocular immunity, development and health. This chapter will cover what is known about how α-MSH is part of the mechanisms of ocular immune privilege, about the expression of melanocortin receptors and the implications of these findings on the role of α-MSH in ocular physiology and its potential use to treat ocular pathologies.
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References
Taylor AW. Ocular immune privilege. Eye 2009. Epub ahead of print (Epub ahead of print).
Medawar P. Immunity to homologous grafted skin. III. the fate of skin homografts transplanted to the brain to subcutaneous tissue and to the anterior chamber of the eye. Br J Exp Path 1948; 29:58–69.
Streilein JW. Ocular immune privilege: therapeutic opportunities from an experiment of nature. Nat Rev Immunol 2003; 3(11):879–889.
Taylor A. A review of the influence of aqueous humor on immunity. Ocul Immunol Inflamm 2003; 11(4):231–241.
Niederkorn JY. The immune privilege of corneal grafts. J Leukoc Biol 2003; 74(2):167–171.
Streilein JW, Masli S, Takeuchi M et al. The eye’s view of antigen presentation. Hum Immunol 2002; 63(6):435–443.
Ferguson TA, Griffith TS. The role of Fas ligand and TNF-related apoptosis-inducing ligand (TRAIL) in the ocular immune response. Chemical Immunology and Allergy 2007; 92:140–154.
Taylor AW, Yee DG, Streilein JW. Suppression of nitric oxide generated by inflammatory macrophages by calcitonin gene-related peptide in aqueous humor. Invest Ophthalmol Vis Sci 1998; 39(8):1372–1378.
Taylor AW, Streilein JW, Cousins SW. Alpha-melanocyte-stimulating hormone suppresses antigen-stimulated T-cell production of gamma-interferon. Neuroimmunomodulation 1994; 1(3):188–194.
Lin HH, Faunce DE, Stacey M et al. The macrophage F4/80 receptor is required for the induction of antigen-specific efferent regulatory T-cells in peripheral tolerance. J Exp Med 2005; 201(10):1615–1625.
Taylor AW, Alard P, Yee DG et al. Aqueous humor induces transforming growth factor-beta (TGF-beta)-producing regulatory T-cells. Curr Eye Res 1997; 16(9):900–908.
Cousins SW, Trattler WB, Streilein JW. Immune privilege and suppression of immunogenic inflammation in the anterior chamber of the eye. Curr Eye Res 1991; 10(4):287–297.
Nishida T, Taylor AW. Specific aqueous humor factors induce activation of regulatory T-cells. Invest Ophthalmol Vis Sci 1999; 40(10):2268–2274.
Granstein R, Staszewski R, Knisely T et al. Aqueous humor contains transforming growth factor-β and a small (<3500 daltons) inhibitor of thymocyte proliferation. Journal of Immunology 1990; 144:3021–3027.
Taylor AW, Streilein JW, Cousins SW. Identification of alpha-melanocyte stimulating hormone as a potential immunosuppressive factor in aqueous humor. Curr Eye Res 1992; 11(12):1199–1206.
Lee TH, Lerner AB, Buettner-Janusch V. The isolation and structure of α-and β-melanocyte-stimulating hormones from monkey pituitary glands. Journal of Biological Chemistry 1961; 236:1390–1394.
Tung YC, Piper SJ, Yeung D et al. A comparative study of the central effects of specific POMC-derived melanocortin peptides on food intake and body weight in Pomc null mice. Endocrinology 2006.
Guijarro A, Laviano A, Meguid MM. Hypothalamic integration of immune function and metabolism. Prog Brain Res 2006; 153:367–405.
Lipton JM, Catania A. Anti-inflammatory actions of the neuroimmunomodulator alpha-MSH. Immunology Today 1997; 18(3):140–145.
Holdeman M, Khorram O, Samson WK et al. Fever-specific changes in central MSH and CRF concentrations. Am J Physiol 1985; 248:R125–R129.
Martin LW, Catania A, Hiltz ME et al. Neuropeptide alpha-MSH antagonizes IL-6-and TNF-induced fever. Peptides 1991; 12:297–299.
Martin LW, Lipton JM. Acute phase response to endotoxin: rise in plasma alpha-MSH and effects of alpha-MSH injection. Am J Physiol 1990; 259(4 Pt 2):R768–772.
Watanabe T, Hiltz ME, Catania A et al. Inhibition of IL-1b-induced periferal inflammation by peripheral and central administration of analogs of the neuropeptide α-MSH. Brain Res Bull 1993; 32:311–314.
Hiltz ME, Catania A, Lipton JM. Alpha-MSH peptides inhibit acute inflammation induced in mice by rIL-1 beta, rIL-6, rTNF-alpha and endogenous pyrogen but not that caused by LTB4, PAF and rIL-8. Cytokine 1992; 4(4):320–328.
Shih ST, Khorram O, Lipton JM et al. Central administration of alpha-MSH antiserum augments fever in the rabbit. Am J Physiol 1986; 250(5 Pt 2):R803–806.
Shih ST, Lipton JM. Intravenous alpha-MSH reduces fever in the squirrel monkey. Peptides 1985; 6(4):685–687.
Chiao H, Foster S, Thomas R et al. Alpha-melanocyte-stimulating hormone reduces endotoxin-induced liver inflammation. J Clin Invest 1996; 97(9):2038–2044.
Cannon JG, Tatro JB, Reichlin S et al. Alpha melanocyte stimulating hormone inhibits immunostimulatory and inflammatory actions of interleukin 1. J Immunol 1986; 137(7):2232–2236.
Catania A, Rajora N, Capsoni F et al. The neuropeptide alpha-MSH has specific receptors on neutrophils and reduces chemotaxis in vitro. Peptides 1996; 17(4):675–679.
Star RA, Rajora N, Huang J et al. Evidence of autocrine modulation of macrophage nitric oxide synthase by alpha-melanocyte-stimulating hormone. Proc Natl Acad Sci USA 1995; 92(17):8016–8020.
Rajora N, Boccoli G, Burns D et al. Alpha-MSH modulates local and circulating tumor necrosis factor-alpha in experimental brain inflammation. J Neurosci 1997; 17(6):2181–2186.
Mason MJ, Van Epps D. Modulation of IL-1, tumor necrosis factor and C5a-mediated murine neutrophil migration by alpha-melanocyte-stimulating hormone. J Immunol 1989; 142(5):1646–1651.
Manna SK, Sarkar A, Sreenivasan Y. Alpha-melanocyte-stimulating hormone down-regulates CXC receptors through activation of neutrophil elastase. Eur J Immunol 2006; 36(3):754–769.
Brzoska T, Kalden DH, Scholzen T et al. Molecular basis of the alpha-MSH/IL-1 antagonism. Ann N Y Acad Sci 1999; 885:230–238.
Ichiyama T, Sakai T, Catania A et al. Inhibition of peripheral NF-kappaB activation by central action of alpha-melanocyte-stimulating hormone. J Neuroimmunol 1999; 99(2):211–217.
Mandrika I, Muceniece R, Wikberg JE. Effects of melanocortin peptides on lipopolysaccharide/ interferon-gamma-induced NF-kappaB DNA binding and nitric oxide production in macrophage-like RAW 264.7 cells: evidence for dual mechanisms of action. Biochemical Pharmacology 2001; 61(5):613–621.
Luger TA. Neuromediators—a crucial component of the skin immune system. Journal of Dermatological Science 2002; 30(2):87–93.
Sarkar A, Sreenivasan Y, Manna SK. Alpha-Melanocyte-stimulating hormone induces cell death in mast cells: involvement of NF-kappaB. FEBS Lett 2003; 549(1–3):87–93.
Teare KA, Pearson RG, Shakesheff KM et al. Alpha-MSH inhibits inflammatory signalling in Schwann cells. Neuroreport 2004; 15(3):493–498.
Cui HS, Hayasaka S, Zhang XY et al. Effect of alpha-melanocyte-stimulating hormone on interleukin 8 and monocyte chemotactic protein 1 expression in a human retinal pigment epithelial cell line. Ophthalmic Res 2005; 37(5):279–288.
Li D, Taylor AW. Diminishment of alpha-MSH anti-inflammatory activity in MC1r siRNA-transfected RAW264.7 macrophages. J Leukoc Biol 2008; 84(1):191–198.
Taylor AW. The immunomodulating neuropeptide alpha-melanocyte stimulating hormone (α-MSH) suppresses LPS-stimulated TLR4 with IRAK-M in macrophages. J Neuroimmunol 2005; 162:43–50.
Grabbe S, Bhardwaj RS, Mahnke K et al. Alpha-Melanocyte-stimulating hormone induces hapten-specific tolerance in mice. J Immunol 1996; 156(2):473–478.
Luger TA, Kalden D, Scholzen TE et al. Alpha-melanocyte-stimulating hormone as a mediator of tolerance induction. Pathobiology 1999; 67(5–6):318–321.
Raap U, Brzoska T, Sohl S et al. Alpha-melanocyte-stimulating hormone inhibits allergic airway inflammation. J Immunol 2003; 171(1):353–359.
Lam CW, Perretti M, Getting SJ. Melanocortin receptor signaling in RAW264.7 macrophage cell line. Peptides 2006; 27(2):404–412.
Taherzadeh S, Sharma S, Chhajlani V et al. alpha-MSH and its receptors in regulation of tumor necrosis factor-alpha production by human monocyte/macrophages. Am J Physiol 1999; 276(5 Pt 2):R1289–1294.
Taylor A, Namba K. In vitro induction of CD25+ CD4+ regulatory T-cells by the neuropeptide alpha-melanocyte stimulating hormone (alpha-MSH). Immunol Cell Biol 2001; 79(4):358–367.
Namba K, Kitaichi N, Nishida T et al. Induction of regulatory T-cells by the immunomodulating cytokines alpha-melanocyte-stimulating hormone and transforming growth factor-beta2. J Leukoc Biol 2002; 72(5):946–952.
Taylor AW. Modulation of regulatory T-cell immunity by the neuropeptide alpha-melanocyte stimulating hormone. Cell Mol Biol (Noisy-le-grand) 2003; 49(2):143–149.
Taylor AW, Kitaichi N, Biros D. Melanocortin 5 receptor and ocular immunity. Cell Mol Biol 2006; 52:141–147.
Kitaichi N, Namba K, Taylor AW. Inducible immune regulation following autoimmune disease in the immune-privileged eye. J Leukoc Biol 2005; 77(4):496–502.
Lindqvist N, Napankangas U, Lindblom J et al. Proopiomelanocortin and melanocortin receptors in the adult rat retino-tectal system and their regulation after optic nerve transection. Eur J Pharmacol 2003; 482(1–3):85–94.
Teshigawara K, Takahashi S, Boswell T et al. Identification of avian alpha-melanocyte-stimulating hormone in the eye: temporal and spatial regulation of expression in the developing chicken. J Endocrinol 2001; 168(3):527–537.
Ringholm A, Fredriksson R, Poliakova N et al. One melanocortin 4 and two melanocortin 5 receptors from zebrafish show remarkable conservation in structure and pharmacology. J Neurochem 2002; 82(1):6–18.
Cerda-Reverter JM, Ling MK, Schioth HB et al. Molecular cloning, characterization and brain mapping of the melanocortin 5 receptor in the goldfish. J Neurochem 2003; 87(6):1354–1367.
Lee DJ, Biros DJ, Taylor AW. Injection of an alpha-melanocyte stimulating hormone expression plasmid is effective in suppressing experimental autoimmune uveitis. Int Immunopharmacol 2009: In press.
Lee TH, Jawan B, Chou WY et al. Alpha-melanocyte-stimulating hormone gene therapy reverses carbon tetrachloride induced liver fibrosis in mice. The Journal of Gene Medicine 2006; 8(6):764–772.
Taylor AW, Kitaichi N. The diminishment of experimental autoimmune encephalomyelitis (EAE) by neuropeptide alpha-melanocyte stimulating hormone (alpha-MSH) therapy. Brain, Behavior and Immunity 2008; 22(5):639–646.
Wang CH, Jawan B, Lee TH et al. Single injection of naked plasmid encoding alpha-melanocyte-stimulating hormone protects against thioacetamide-induced acute liver failure in mice. Biochem Biophys Res Commun 2004; 322(1):153–161.
Ceriani G, Diaz J, Murphree S et al. The neuropeptide alpha-melanocyte-stimulating hormone inhibits experimental arthritis in rats. Neuroimmunomodulation 1994; 1(1):28–32.
Delgado Hernandez R, Demitri MT, Carlin A et al. Inhibition of systemic inflammation by central action of the neuropeptide alpha-melanocyte-stimulating hormone. Neuroimmunomodulation 1999; 6(3):187–192.
Nishida T, Miyata S, Itoh Y et al. Anti-inflammatory effects of alpha-melanocyte-stimulating hormone against rat endotoxin-induced uveitis and the time course of inflammatory agents in aqueous humor. Int Immunopharmacol 2004; 4(8):1059–1066.
Shiratori K, Ohgami K, Ilieva IB et al. Inhibition of endotoxin-induced uveitis and potentiation of cyclooxygenase-2 protein expression by alpha-melanocyte-stimulating hormone. Invest Ophthalmol Vis Sci 2004; 45(1):159–164.
Ng TF, Kitaichi N, Taylor AW. In vitro generated autoimmune regulatory T-cells enhance intravitreous allogeneic retinal graft survival. Invest Ophthalmol Vis Sci 2007; 48(11):5112–5117.
Gatti S, Colombo G, Buffa R et al. alpha-Melanocyte-stimulating hormone protects the allograft in experimental heart transplantation. Transplantation 2002; 74(12):1678–1684.
Caspi R, Roberge F, Chan C et al. A new model of autoimmune disease, experimental autoimmune uveoretinitis induced in mice with two different retinal antigens. Journal of Immunology 1988; 140:1490–1495.
Taylor AW, Yee DG, Nishida T et al. Neuropeptide regulation of immunity. The immunosuppressive activity of alpha-melanocyte-stimulating hormone (alpha-MSH). Ann NY Acad Sci 2000; 917:239–247.
Ohta K, Yamagami S, Taylor AW et al. IL-6 antagonizes TGF-beta and abolishes immune privilege in eyes with endotoxin-induced uveitis. Invest Ophthalmol Vis Sci 2000; 41(9):2591–2599.
Naveh N, Marshall J. Melanocortins are comparable to corticosteroids as inhibitors of traumatic ocular inflammation in rabbits. Graefes Arch Clin Exp Ophthalmol 2001; 239(11):840–844.
Naveh N. Melanocortins applied intravitreally delay retinal dystrophy in Royal College of Surgeons rats. Graefes Arch Clin Exp Ophthalmol 2003; 241(12):1044–1050.
Naveh N, Kaplan-Messas A, Marshall J. Mechanism related to reduction of intraocular pressure by melanocortins in rabbits. Br J Ophthalmol 2000; 84(12):1411–1414.
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Taylor, A.W., Lee, D. (2010). Applications of the Role of α-MSH in Ocular Immune Privilege. In: Catania, A. (eds) Melanocortins: Multiple Actions and Therapeutic Potential. Advances in Experimental Medicine and Biology, vol 681. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-6354-3_12
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DOI: https://doi.org/10.1007/978-1-4419-6354-3_12
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