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)

We postulate that wound healing is an orderly process mediated by a programmed expression of cytokines and growth factors. We suggest that these factors are produced in a consistent sequence, in regulated quantities and eliminated when their function is complete. We report here the results of studies on several cytokines, growth factors and the intercellular adhesion molecule expressed during the healing of grafts were visible clinically around 3-5 days post-graft and were completed by 4 weeks post-graft. During the 1st 2 weeks, we observed the following. (i) K-14 keratin was prominent throughout the entire epidermis. Thereafter it was limited to basal cell layers. (ii) Langerhans cells were not detectable with anti-human CD1a antibodies during the first week of healing but were clearly detectable 2 weeks post-graft. (iii) DOPA (dihydroxy phenylalanine) positive melanocytes gradually increased with time. The epidermis 21 to 28 days post-graft clinically and histologically seemed to be morphologically intact. Interleukin-1 (IL-1) was clearly detected in some basal cells of the epidermis, especially in melanocytes and some keratinocytes during the early stage of healing. Transforming growth factor-alpha (TGF-alpha) was detected in epidermis first in melanocytes and some keratinocytes shortly after grafting and again in the late stage of healing. It was also found in some dermal cells. Its expression coincided with keratinocyte proliferation and melanocyte migration. TGF-beta was strongly expressed in the epidermis and dermis after the first week post graft. (iv) ICAM-1 was transiently expressed only at the onset of healing. We previously reported that pro-opiomelanocortin and its derivatives MSH/ ACTH are expressed strongly during the healing of human xenografts. The 4 additional molecules which are the subject of this report all are expressed in healing human skin in a predictable sequence and quantity (intensity of stain). Together these data support our hypothesis that healing is a highly regulated process mediated by numerous cytokines.
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PMID:The expression of cytokines, growth factors and ICAM-1 in the healing of human cutaneous xenografts on nude mice. 906 2

We investigated the effect of acute and chronic stress on growth hormone (GH) plasma levels in rats. Acute stress was provoked by intravenous administrations of IL-1 beta and TNF-alpha. Determinations were made at 10, 30, 60, 120 and 180 min following i.v. injection of these cytokines into the caudal vein. We also investigated the chronic stress induced by hind paw injections of Freund's adjuvant. Arthritis was developed by 21 days following such injection. GH levels were studied at 7, 14 and 21 days after induction of arthritis on several blood samples which were withdrawn from tail veins, and long-term hormonal profiles (3 hours' sampling) were determined at 12.00 am, 1.30 pm and 3.00 pm. Local administration of dexamethasone and the monoclonal antibody anti-ICAM-1 were also used in arthritic rats. Following acute stress, a significant reduction of plasma GH levels has been evidenced, possibly related to the stimulation of corticotropin-releasing hormone. Following chronic stress, we demonstrated a significant increase of GH levels, which were significantly reduced by dexamethasone treatment and to a lesser extent by anti-ICAM-1 administration.
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PMID:Effect of acute and chronic inflammation on plasma growth hormone levels in rats. 940 72

Alpha-MSH, a proopiomelanocortin (POMC)-derived peptide, is known to be produced in the pituitary, the skin, and melanoma tumors and to possess many biological effects, mainly on melanocyte pigmentation and growth. Moreover, the melanocyte expresses adhesion molecules, including ICAM-1. The latter has been reported to play a role in melanoma spread and associated metastatic process. We conducted a study in order to evaluate the possible effect of MSH on ICAM-1 expression in human cultured malignant and normal melanocytes. Our data show that alpha-MSH inhibits ICAM-1 expression stimulated by TNF in a concentration-dependent manner, both at the protein and gene expression level. Ninety percent inhibition was obtained with 10 nM MSH, while 50% inhibition was achieved with 1 nM. Endogenous cAMP elevation with forskolin as well as an exogenous cAMP stable analogue (Sp-cAMPS) produced the same inhibitory effect. A screening of malignant melanocytes showed that inhibition of ICAM-1 expression could be achieved only in those cells expressing detectable MSH receptors and seemed to correlate with the number of binding sites. In conclusion, our data strongly suggest alpha-MSH as a potent inhibitor of ICAM-1 expression in malignant melanocytes acting through MSH receptor stimulation and subsequent cAMP increase.
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PMID:Modulation of ICAM-1 expression by alpha-MSH in human melanoma cells and melanocytes. 957 72

The immune, neural, and endocrine systems do not act autonomously; rather, multiple communicative pathways exist among the nervous, endocrine, and immune systems that facilitate physiological immunoregulation. Patients with spinal cord injury (SCI) have decreased natural and adaptive immune responses by 2 weeks after injury. In patients with SCI, adrenocorticotropic hormone (ACTH) and urine-free cortisol levels were increased while zinc and albumin levels were decreased, respectively. In addition, the surface markers alpha 2, alpha 3, alpha 4, CD11a, CD11b, CD18, CD54, and CD8 found on lymphocytes and alpha 3, alpha 4, CD11a, CD18, and CD8 surface markers found on granulocytes were also decreased in the patient population. Finally, the adhesion molecules binding ability in the SCI group was also decreased when compared with a control group. Overall, the investigation showed that patients with SCI have a decreased immune function, especially succeeding the SCI injury, an impaired nutrition status, and a decreased number of adhesion molecules, all of which contribute to delayed wound healing.
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PMID:Review of immune function, healing of pressure ulcers, and nutritional status in patients with spinal cord injury. 1091 54

The hypothalamic-pituitary-adrenal (HPA) axis is the major stress response system. Several components of the HPA axis, such as corticotropin-releasing hormone (CRH) and POMC peptides and their receptors are also present in the skin. In earlier studies, we showed that CRH inhibits cellular proliferation of immortalized human keratinocytes. We now examine further the functional activity of the HPA axis in the skin, by characterizing the actions of CRH on normal foreskin keratinocytes. The CRH receptor was detected as CRH-R1 antigen at 47 kDa in the cultured keratinocytes by Western blotting, and immunohistochemistry demonstrated its presence in the epidermal and follicular keratinocytes. CRH is also biologically active in cultured keratinocytes, where it inhibits proliferation and enhances the interferon-gamma-stimulated expression of the hCAM and ICAM-1 adhesion molecules and of the HLA-DR antigen. These effects were concentration-dependent, with maximal activity at CRH 10(-7) M. Thus, in the keratinocyte, the most important cellular component of the epidermis, CRH appears to induce a shift in energy metabolism away from proliferation activity, and toward the enhancement of immunoactivity. Therefore, similar to its central actions, cutaneous CRH may also he involved in the stress response, but at a highly localized level.
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PMID:Pleiotropic effects of corticotropin releasing hormone on normal human skin keratinocytes. 1124 6

Pain can be effectively controlled by endogenous mechanisms based on neuroimmune interactions. In inflamed tissue immune cell-derived opioid peptides activate opioid receptors on peripheral sensory nerves leading to potent analgesia. This is brought about by a release of opioids from inflammatory cells after stimulation by stress or corticotropin-releasing hormone (CRH). Immunocytes migrate from the circulation to inflamed tissue in multiple steps, including their rolling, adhesion, and transmigration through the vessel wall. This is orchestrated by adhesion molecules on leukocytes and vascular endothelium. Intercellular adhesion molecule-1 [ICAM-1 (or CD54)] is expressed by endothelium and mediates adhesion and extravasation of leukocytes. The goal of this study was to show that ICAM-1 regulates the homing of opioid-producing cells and the subsequent generation of analgesia within sites of painful inflammation. This was accomplished using immunofluorescence, flow cytometry, and behavioral (paw pressure) testing. We found that ICAM-1 is upregulated on the vascular endothelium, simultaneously with an enhanced immigration of opioid-containing immune cells into inflamed paw tissue. The intravenous administration of a monoclonal antibody against ICAM-1 markedly decreased the migration of opioid-containing leukocytes and of granulocytes, monocytes-macrophages, and T cells to the inflamed tissue. At the same time, circulating immunocytes increased in numbers, and macroscopic inflammation (hyperalgesia, paw volume, and paw temperature) remained primarily unchanged. Most importantly, peripheral opioid analgesia elicited either by cold water swim stress or by intraplantar administration of CRH was dramatically reduced. Together, these findings indicate that ICAM-1 expressed on vascular endothelium recruits immunocytes containing opioids to promote the local control of inflammatory pain.
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PMID:Opioid control of inflammatory pain regulated by intercellular adhesion molecule-1. 1209 10

The neuroendocrine hormone alpha-melanocyte stimulating hormone (MSH) has profound antiinflammatory and immunomodulating properties. Here we have examined the possibility that alpha-MSH may interfere with the expression and function of cell adhesion molecules (CAMs) expressed by human dermal microvascular endothelial cells (HDMECs) in response to lipopolysaccharide (LPS) or TNFalpha in vitro and in vivo. In HDMEC, alpha-MSH (10(-8)/10(-12) M) profoundly reduced the mRNA and protein expression of E-selectin, vascular CAM (VCAM)-1, and intercellular CAM (ICAM)-1 induced by LPS or TNFalpha as determined by semiquantitative RT-PCR, ELISA, and fluorescence-activated cell sorter analysis. In addition, alpha-MSH significantly impaired the LPS-induced ICAM-1 and VCAM-1-mediated adhesion of lymphocytes to HDMEC monolayer in a functional adhesion assay. Likewise, alpha-MSH effectively inhibited the transcription factor nuclear factor-kappaB activation in HDMEC, which is required for CAM gene expression. Importantly in vivo, in murine LPS-induced cutaneous vasculitis (local Shwartzman reaction), a single ip injection of alpha-MSH significantly suppressed the deleterious vascular damage and hemorrhage by inhibiting the sustained expression of vascular E-selectin and VCAM-1. This persistent expression has been implicated in the dysregulation of diapedesis and activation of leukocytes, which subsequently leads to hemorrhagic vascular damage. Our findings indicate that alpha-MSH may have an important therapeutical potential for the treatment of vasculitis, sepsis, and inflammatory diseases.
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PMID:Alpha-melanocyte stimulating hormone prevents lipopolysaccharide-induced vasculitis by down-regulating endothelial cell adhesion molecule expression. 1248 65

There is a substantial body of evidence that the tridecapeptide alpha-melanocyte-stimulating hormone (alpha-MSH) functions as a mediator of immunity and inflammation. The immunomodulating capacity of alpha-MSH is primarily because of its effects on melanocortin receptor (MC-1R)-expressing monocytes, macrophages, and dendritic cells (DCs). alpha-MSH down-regulates the production of proinflammatory and immunomodulating cytokines (IL-1, IL-6, TNF-alpha, IL-2, IFN-gamma, IL-4, IL-13) as well as the expression of costimulatory molecules (CD86, CD40, ICAM-1) on antigen-presenting DCs. In contrast, the production of the cytokine synthesis inhibitor IL-10 is up-regulated by alpha-MSH. At the molecular level, these effects of alpha-MSH are mediated via the inhibition of the activation of transcription factors such as NFkappaB. Not only alpha-MSH but also its C-terminal tripeptide (alpha-MSH 11-13, KPV) was able to bind to MC-1R and to modulate the function of APCs. In vivo, using a mouse model of contact hypersensitivity (CHS) systemic and topical application of alpha-MSH or KPV inhibited the sensitization and the elicitation phase of CHS and was able to induce hapten-specific tolerance. To investigate the underlying mechanisms of tolerance induction, we have performed in vivo transfer experiments. Treatment of naive mice with bone marrow-derived immature haptenized and alpha-MSH-pulsed DCs resulted in a significant inhibition of CHS. Furthermore, tolerance induction was found to be mediated by the generation of CTLA4(+) and IL-10-producing T lymphocytes. The potent capacity of alpha-MSH to modulate the function of antigen-presenting cells (APCs) has been further supported in another experimental approach. In vitro, by activating APCs, alpha-MSH has been shown to modulate IgE production by IL-4 and anti-CD40 stimulated B lymphocytes. Moreover, in a murine model of allergic airway inflammation, systemic treatment with alpha-MSH resulted in a significant reduction of allergen-specific IgE production, eosinophil influx, and IL-4 production. These effects were mediated via IL-10 production, because IL-10 knockout mice were resistant to alpha-MSH treatment. Therefore, therapeutic application of alpha-MSH or related peptides (KPVs) as well as alpha-MSH/KPV-pulsed DCs may be a useful approach for the treatment of inflammatory, autoimmune, and allergic diseases in the future.
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PMID:New insights into the functions of alpha-MSH and related peptides in the immune system. 1285 8

Psychosocial factors have been reported to be independently associated with coronary heart disease (CHD). Though corticotropin-releasing hormone (CRH) is the major hormone activated during adaptive responses to stressful stimuli, the undergoing pathophysiological mechanism related to stress-induced endothelial dysfunction is still poorly understood. This study sought to investigate the effects of extrahypothalamic CRH on monocyte/endothelium adhesion. Second we elucidate the influence of CRH on monocytic endothelin-1 (ET-1) and nitric oxide (NO) release and the receptors involved. Cell adhesion was determined using an adhesion assay, MAC-1 expression by flow cytometry. ET-1/NO release were quantified via ELISA or fluorometrically, monocytic CRH-receptors were confirmed by mRNA. Corticotropin-releasing hormone induced a significant time- and concentration-dependent increase of cell adhesion as well as monocytic MAC-1 expression; endothelial ICAM-1 and VCAM-1 expression was not altered. In addition, corticotropin-releasing hormone significantly increased monocytic ET-1 release whereas nitric oxide release was decreased. The effect was abolished by the selective CRH-receptor antagonist astressin. Our findings support the importance of peripherally circulating corticotropin-releasing hormones, by influencing specific homeostatic properties of monocytes. Our data may provide a novel concept of how specific CRH-receptor antagonists may prevent CRH (stress)-related endothelial dysfunction up to cardiovascular complications.
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PMID:Effects of corticotropin-releasing hormone (CRH) on monocyte function, mediated by CRH-receptor subtype R1 and R2: a potential link between mood disorders and endothelial dysfunction? 1642 94

Adoptive immunotherapy for melanoma appears to be a promising approach. The aim of our study was to discuss the role of "tumour tissue" immunogenicity in response to adoptive immunotherapy. We thus studied the potential correlation between the expression of some melanocyte differentiation antigens, adhesion molecules and cytokines expressed by the tumour cells and the survival of patients receiving an adoptive immunotherapy with autologous Tumour Infiltrating Lymphocytes (TIL). An immunohistochemical study was performed on the lymph node samples obtained from 38 patients who received autologous TIL plus interleukin-2. Frozen sections were immunostained for melanocyte differentiation antigens (Melan-A and gp100), MHC molecules (Class I and II), adhesion molecules (ICAM-1, LFA-3) and suppressive cytokines (IL-10, TGF-beta and alpha-MSH). Expression levels of each marker were evaluated using a semi-quantitative visual scale. Using a multivariate analysis, a low expression level of TGF-beta by tumour cells was significantly associated with a prolonged relapse-free survival. A low expression level of TGF-beta, IL-10, ICAM-1 and alpha-MSH by tumour cells was significantly associated with a longer overall survival. This work suggests that a weak expression of immunosuppressive cytokines (IL-10, TGF-beta and alpha-MSH) could be a favourable prognostic marker for patients receiving autologous TIL.
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PMID:Tissue prognostic markers for adoptive immunotherapy in melanoma. 1754 Jun 35


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