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)

Eighteen patients treated with prednisone on alternate days for varying degrees of alopecia areata (AA) were examined a mean of 15 months after discontinuation of the drug. Despite an initial response to the therapy, long-term benefit was not thought to be substantial. Numerous side effects related either to systemic corticosteroids or to AA were apparent during the course of therapy, as well as at the time of the evaluation reported herein. Acne, obesity, lenticular opacities, mild hypertension, and impaired adrenocorticotropic hormone (ACTH) reserve were among the findings noted. Long-term treatment was not accompanied by an obvious beneficial change in the natural course of AA. Because of the potentially serious side effects and the lack of substantial improvement in the eventual course, alternate-day prednisone therapy is not recommended for long-term use in AA.
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PMID:Prednisone therapy for alopecia areata. A follow-up report. 79 Nov 52

This essay reviews the available evidence that the proximal hair follicle epithelium generates and maintains an area of relative immune privilege during a defined segment of the hair cycle (i.e., during anagen). This immune privilege is chiefly characterized by a very low level of expression of MHC class Ia antigens and by the local production of potent immunosuppressive agents, such as alpha-MSH and TGF-beta1. We discuss the putative functions of immune privilige of the anagen hair bulb, favoring the view that immune privilege serves mainly to sequester anagen- and/or melanogenesis-associated autoantigens from immune recognition by autoreactive CD8+ T cells. On this basis, we develop how the "immune privilege collapse model" of alopecia areata pathogenesis was conceived. In our discussion of the clinical implications of immune privilege, we outline the currently available evidence in support of this still hypothetical scenario to explain the initiation, progression, and termination of alopecia areata lesions. We review the most recent evidence from our laboratory that alpha-MSH, IGF-1, and TGF-beta1 can downregulate IFN-gamma-induced ectopic MHC class I expression in human anagen hair bulbs in vitro. Finally, we suggest that hair follicle-derived alpha-MSH, IGF-gamma, and TGF-beta1 form part of a constitutively active "IP restoration machinery" of the anagen hair bulb, which we propose to be recruited whenever the hair follicle suffers immune injury. Finally, we sketch some particularly promising avenues for future investigation into the far too long ignored hair follicle immune privilege.
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PMID:The hair follicle and immune privilege. 1458 71

The collapse of major histocompatibility complex (MHC) class-I-dependent immune privilege can lead to autoimmune disease or fetal rejection. Pragmatic and instructive models are needed to clarify the as yet obscure controls of MHC class I down-regulation in situ, to dissect the principles of immune privilege generation, maintenance, and collapse as well as to develop more effective strategies for immune privilege restoration. Here, we propose that human scalp hair follicles, which are abundantly available and easily studied, are ideally suited for this purpose: interferon-gamma induces ectopic MHC class I expression in the constitutively MHC class-I-negative hair matrix epithelium of organ-cultured anagen hair bulbs, likely via interferon regulatory factor-1, along with up-regulation of the MHC class I pathway molecules beta(2)microglobulin and transporter associated with antigen processing (TAP-2). In the first report to identify natural immunomodulators capable of down-regulating MHC class I expression in situ in a normal, neuroectoderm-derived human tissue, we show that ectopic MHC class I expression in human anagen hair bulbs can be normalized by treatment with alpha-MSH, IGF-1, or TGF-beta1, all of which are locally generated, as well as by FK506. These agents are promising candidates for immune privilege restoration and for suppressing MHC class I expression where this is clinically desired (eg, in alopecia areata, multiple sclerosis, autoimmune uveitis, mumps orchitis, and fetal or allograft rejection).
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PMID:Collapse and restoration of MHC class-I-dependent immune privilege: exploiting the human hair follicle as a model. 1474 67

Understanding how selected tissue sites establish immune privilege (IP) is of interest to both basic immunology and clinical medicine: it provides novel insights into autoimmunity, fetal and allotransplant rejection and tumor escape from immunosurveillance. Here, we review why the hair follicle can serve as a uniquely accessible, widely available and instructive model for studying the establishment, maintenance, collapse and restoration of IP. The hair follicle epithelium rhythmically generates, maintains and deconstructs an area of relative IP, characterized by very low expression of MHC Ia and suppressed MHC II-dependent antigen presentation, accompanied by the local production of potent immunosuppressants capable of downregulating MHC I (e.g. transforming growth factor-beta1, alpha-melanocyte-stimulating hormone). We discuss the physiological functions of hair follicle IP, illustrate its clinical and therapeutic relevance by focusing on alopecia areata, an autoimmune hair loss disorder, and outline important unanswered questions for future research into one of nature's most intriguing and abundant, yet commonly ignored, sites of IP.
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PMID:A 'hairy' privilege. 1562 7

Psychological factors are believed to play a role in the pathogenesis of alopecia areata (AA), a frequently encountered hair disorder. In our study, statistically significant elevation of psychological stress was felt by AA patients prior hair loss compared with control, which was strongly believed contributory to hair loss (t-test, P < 0.01). The corticotropin-releasing hormone (CRH) and proopiomelanocortin (POMC) mRNA have been identified in the basal layer of the epidermis and pilosebaceous units of the normal scalp. And with the recent discovery of melanocytes and dermal fibroblasts capable of corticosterone production, the presence of a local stress response system resembling the hypothalamic-pituitary-adrenal (HPA) axis has been suggested. The local stress response system is involved in regulation of the normal hair cycle, but its precise role in AA is unknown. The influence of a local HPA axis or rather, CRH-POMC axis in AA was investigated by analysing immunohistochemically the expression levels of CRH and POMC peptides, including the adrenocorticotropic hormone (ACTH) and alpha-melanocyte-stimulating hormone (alpha-MSH), in a number of AA lesions and normal scalp (as control). The epidermis and pilosebaceous units of normal scalp stained weakly with CRH, ACTH and alpha-MSH, whereas those from the affected sites of the AA group showed intense expression of the peptides (chi-square test, P < 0.01). The meaning of this enhanced expression and their role in the pathogenesis of AA should be further evaluated in future.
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PMID:Immunoreactivity of corticotropin-releasing hormone, adrenocorticotropic hormone and alpha-melanocyte-stimulating hormone in alopecia areata. 1676 60

Perceived stress has long been allied with disturbances of the dynamic equilibrium established between the nervous, endocrine and immune systems, thus triggering or aggravating disease manifestation. Several common skin diseases are now acknowledged to be worsened by psychological stress, particularly immunodermatoses such as atopic dermatitis, psoriasis, seborrheic eczema, prurigo nodularis, lichen planus, chronic urticaria, alopecia areata and pruritus sine materia. Itch (pruritus) is perhaps the most common symptom associated with a majority of these inflammatory skin diseases, and acute as well as chronic stress perceptions are recognized to trigger or enhance pruritus. A wealth of mediators released systemically or locally in the skin in response to stress increase sensory innervation, upregulate the production of other pruritogenic agents, perpetuate (neurogenic) inflammation and lower the itch threshold. In the present review, we explore recent frontiers in both stress and pruritus research and portray the perpetuation of chronic skin inflammation and itch as a neuroendocrine-immune 'misalliance'. We argue that key candidate molecules of the stress response with strong pruritogenic potential, such as nerve growth factor, corticotropin-releasing hormone and substance P, and mast cells, which may be considered as 'central cellular switchboards of pruritogenic inflammation', need to be further explored systematically in order to develop more effective therapeutic combination strategies for itch management in chronic, stress-vulnerable inflammatory skin diseases.
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PMID:From the brain-skin connection: the neuroendocrine-immune misalliance of stress and itch. 1770 57

The relationship of the stress response to the pathogenesis of alopecia areata (AA) was investigated by subjecting normal and skin graft-induced, AA-affected C3H/HeJ mice to light ether anesthesia or restraint stress. Plasma corticosterone (CORT), adrenocorticotropic hormone (ACTH), and estradiol (E2) levels were determined by RIA, whereas gene expression in brains, lymphoid organs, and skin was measured by quantitative RT-PCR for corticotropin-releasing hormone (Crh), arginine vasopressin (Avp), proopiomelanocortin (Pomc), glucocorticoid receptor (Nr3c1), mineralocorticoid receptor (Nr3c2), corticotropin-releasing hormone receptor types 1 and 2 (Crhr1, Crhr2), interleukin-12 (Il12), tumor necrosis factor-alpha (Tnf alpha), and estrogen receptors type-1 (Esr1) and type-2 (Esr2). AA mice had a marked increase in hypothalamic-pituitary-adrenal (HPA) tone and activity centrally, and peripherally in the skin and lymph nodes. There was also altered interaction between the adrenal and gonadal axes compared with that in normal mice. Stress further exacerbated changes in AA mouse HPA activity both centrally and peripherally. AA mice had significantly blunted CORT and ACTH responses to acute ether stress (physiological stressor) and a deficit in habituation to repeated restraint stress (psychological stressor). The positive correlation of HPA hormone levels with skin Th1 cytokines suggests that altered HPA activity may occur as a consequence of the immune response associated with AA.
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PMID:Development of alopecia areata is associated with higher central and peripheral hypothalamic-pituitary-adrenal tone in the skin graft induced C3H/HeJ mouse model. 1943 88

Human skin expresses elements of the hypothalamo-pituitary-adrenal (HPA) axis that function as a local stress response system. Because adrenocorticotropic hormone (ACTH) is an intermediate in the HPA axis from corticotropin-releasing hormone (CRH) signal to cortisol secretion, MC2R that binds only ACTH may be important in the stress response of skin. We investigated the local expression of MC2R by immunohistochemistry to identify the role of ACTH/MC2R in stress-associated alopecia areata (AA). MC2R appeared to be highly compartmentalized in scalp skin including the epidermal cells of hair follicles and epidermis, sebaceous and eccrine glands, as well as dermal fibroblasts. The expression of MC2R was lower in AA lesions than in normal scalp tissue in almost all scalp skin cells, especially in epithelial cells. These findings demonstrate that MC2R expression is aberrant in AA and suggest a deficit in ACTH/MC2R activity may play an important role in the pathophysiology of AA.
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PMID:Melanocortin receptor type 2 (MC2R, ACTH receptor) expression in patients with alopecia areata. 2059 Aug 21

Alopecia areata (AA) is a hair follicle-specific autoimmune disease that is inherited genetically but triggered environmentally. Stress response is believed to play a role in the pathogenesis of AA. The hypothalamic-pituitary-adrenal axis (HPA axis), known as the stress axis, plays a cardinal role in the stress response. Growing evidence demonstrates that stress responses are under the control of both the central and peripheral nervous systems. Skin and hair follicles display peripheral HPA axis-like signaling systems. Some studies have revealed that a modified HPA axis, which is characterized by enhanced CRH/CRHR and insufficient glucocorticoid, is involved in the pathology of AA, suggesting that the paradoxical expression differs from that of normal control and should be further examined. Because adrenocorticotropic hormone (ACTH) is an intermediary in the HPA axis, MC2R, which specifically binds ACTH, may be important in the stress response of skin. Therefore, we investigated the gene and protein expression of MC2R in AA lesions and tried to elucidate the connection between HPA axis regulation, MC2R and AA. Reciprocal changes in MC2R mRNA and proteins in human AA were observed in our study; while mRNA levels were higher in lesions from AA patients compared with scalp tissues from normal controls, protein levels of MC2R were lower. The paradoxical expression of MC2R gene and protein levels coincided with evidence that over-responsive HPA activity coexists with a deficient HPA response in AA. We hypothesized that the HPA axis response in human AA may be the following: stressors first activate excess CRH/CRHR to produce increased ACTH, which up-regulates the expression of MC2R mRNA, but the stress response cannot create sufficient cortisol when the binding of ACTH/MC2R is deficient due to decreased MC2R protein. This hypothesis rationally clarifies the changed HPA axis in human AA and highlights the importance of MC2R in the pathogenesis of AA. The inconsistent expression of protein and mRNA implicates post-transcriptional control of human MC2R gene expression as found in murine MC2R gene.
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PMID:An implication for post-transcriptional control: reciprocal changes of melanocortin receptor type 2 mRNA and protein expression in alopecia areata. 2088 25

Alopecia areata (AA) is a chronic autoimmune hair loss disease that affects several million men, women and children worldwide. Previous studies have suggested a link between autoimmunity, stress hormones, and increased cardiovascular disease risk. In the current study, histology, immunohistology, quantitative PCR (qPCR) and ELISAs were used to assess heart health in the C3H/HeJ mouse model for AA and heart tissue response to adrenocorticotropic hormone (ACTH) exposure. Mice with AA exhibited both atrial and ventricular hypertrophy, and increased collagen deposition compared to normal-haired littermates. QPCR revealed significant increases in Il18 (4.6-fold), IL18 receptor-1 (Il18r1; 2.8-fold) and IL18 binding protein (Il18bp; 5.2-fold) in AA hearts. Time course studies revealed a trend towards decreased Il18 in acute AA compared to controls while Il18r1, Il18bp and Casp1 showed similar trends to those of chronic AA affected mice. Immunohistochemistry showed localization of IL18 in chronic AA mouse atria. ELISA indicated cardiac troponin-I (cTnI) was elevated in the serum and significantly increased in AA heart tissue. Cultures of heart atria revealed differential gene expression between AA and control mice in response to ACTH. ACTH treatment induced significant increase in cTnI release into the culture medium in a dose-dependent manner for both AA and control mice. In conclusion, murine AA is associated with structural, biochemical, and gene expression changes consistent with cardiac hypertrophy in response to ACTH exposure.
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PMID:Development of autoimmune hair loss disease alopecia areata is associated with cardiac dysfunction in C3H/HeJ mice. 2365 56


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