Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Immune privilege in the eye is believed to originate from the eye's need to avoid the sight-destroying consequences of inflammation. Over the past 25 years, many of the anatomical, cellular, and molecular mechanisms by which the eye avoids inflammation secondary to adaptive immune responses have been elucidated. In the recent past, it has become increasingly clear that innate immune responses play a critical role in activating the adaptive immune response. Moreover, innate immunity itself carries a heavy burden of inflammation, thereby posing a threat to vision if it should occur intraocularly. Ocular immunologists have now begun to inquire into the extent to which the eye regulates the expression of innate immunity in oculi. Evidence is presented which indicates that factors found in normal aqueous humor (1) prevent NK cells from lysing their targets, (2) inhibit neutrophil activation by CD95 ligand, (3) suppress nitric oxide production by activated macrophages, and (4) interfere with complement activation via the alternative pathway. These factors include transforming growth factor-beta2, alpha-melanocyte-stimulating hormone, calcitonin gene-related peptide, and migration inhibitory factor. The ability of the eye to prevent intraocular activation of innate immune effectors spares the corneal endothelium (which expresses CD95 ligand constitutively, but low levels of MHC class I molecules) from destruction by NK cells and neutrophils, and protects the visual axis from distortion by macrophage and complement-mediated inflammation. Thus, privilege exists in the eye for both adaptive and innate immunity.
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PMID:Does innate immune privilege exist? 1077 Feb 79

It has been recognized for over a century that the eye is endowed with remarkable properties that permit the long-term survival of foreign tumor and tissue grafts that are normally rejected at extraocular sites. This ocular immune privilege was originally attributed to a putative sequestration of antigens in the eye as a result of the conspicuous absence of intraocular lymphatic drainage channels. In the last 30 years, a sizeable body of information indicates that ocular immune privilege is a product of multiple anatomical, physiological, and immunoregulatory processes. Ocular tissues and fluids express a wide variety of anti-inflammatory and immunosuppressive molecules, including CD95L (FasL), transforming growth factor-beta, macrophage migration inhibitory factor, alpha-melanocyte-stimulating hormone, calcitonin gene-related peptide, somatostatin, and complement regulatory proteins. Moreover, antigens entering the anterior chamber of the eye evoke a unique form of immune deviation that culminates in the antigen-specific suppression of TH1 immune responses. Finally, the intraocular milieu contains both cell membrane and soluble factors that inhibit both the adaptive and innate immune systems. The hair follicle is also recognized for its immune privilege. Like the anterior chamber of the eye, it produces anti-inflammatory and immunosuppressive cytokines, such as transforming growth factor-beta and adrenocorticotrophic hormone. The cells of the hair follicle display limited expression of class Ia MHC molecules and, like cells that line the anterior chamber of the eye, are protected against CD8+ cytotoxic T lymphocyte attack. Gaining a better understanding of the immune privilege of the hair follicle may provide insights into the regulation and pathogenesis of immune-mediated diseases of the skin.
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PMID:Mechanisms of immune privilege in the eye and hair follicle. 1458 67

Ultraviolet radiation is a well established epidemiologic risk factor for malignant melanoma. This observation has been linked to the relative resistance of normal melanocytes to ultraviolet B (UVB) radiation-induced apoptosis, which consequently leads to accumulation of UVB radiation-induced DNA lesions in melanocytes. Therefore, identification of physiologic factors regulating UVB radiation-induced apoptosis and DNA damage of melanocytes is of utmost biological importance. We show that the neuropeptide alpha-melanocyte-stimulating hormone (alpha-MSH) blocks UVB radiation-induced apoptosis of normal human melanocytes in vitro. The anti-apoptotic activity of alpha-MSH is not mediated by filtering or by induction of melanin synthesis in melanocytes. alpha-MSH neither leads to changes in the cell cycle distribution nor induces alterations in the expression of the apoptosis-related proteins Bcl(2), Bcl(x), Bax, p53, CD95 (Fas/APO-1), and CD95L (FasL). In contrast, alpha-MSH markedly reduces the formation of UVB radiation-induced DNA damage as demonstrated by reduced amounts of cyclobutane pyrimidine dimers, ultimately leading to reduced apoptosis. The reduction of UV radiation-induced DNA damage by alpha-MSH appears to be related to induction of nucleotide excision repair, because UV radiation-mediated apoptosis was not blocked by alpha-MSH in nucleotide excision repair-deficient fibroblasts. These data, for the first time, demonstrate regulation of UVB radiation-induced apoptosis of human melanocytes by a neuropeptide that is physiologically expressed within the epidermis. Apart from its ability to induce photoprotective melanin synthesis, alpha-MSH appears to exert the capacity to reduce UV radiation-induced DNA damage and, thus, may act as a potent protection factor against the harmful effects of UV radiation on the genomic stability of epidermal cells.
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PMID:alpha-Melanocyte-stimulating hormone protects from ultraviolet radiation-induced apoptosis and DNA damage. 1556 80