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)

Intracerebroventricular (ICV) injections of interleukin-1 beta (IL-1 beta) produced a dose-dependent increase in plasma corticosterone and adrenocorticotropic hormone (ACTH) within 2 hr of injection and then declined over the next 24 hr. Using a potent steroidogenic dose of IL-1 beta (5 ng), ICV injection resulted in suppression of splenic macrophage IL-1 secretion following stimulation by LPS in vitro. Macrophage TGF-beta secretion was not affected, indicating a differential action of ICV IL-1 beta on macrophage cytokine production. Following adrenalectomy (ADX), the suppressive effect of ICV IL-1 beta was reversed and resulted in stimulation of macrophage IL-1 secretion, indicating that the suppression was mediated by adrenocorticol activation. However, surgical interruption of the splenic nerve to eliminate autonomic innervation of the spleen also prevented the macrophage suppressive signal in rats given ICV IL-1 beta. Furthermore, the combination of ADX and splenic nerve section resulted in a potent stimulatory effect of ICV IL-1 beta on splenic macrophage IL-1 secretion which was greater than either ADX or splenic nerve section alone. These results support the concept of a negative feedback on macrophage IL-1 secretion by the central action of IL-1 beta and indicate that both the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system mediate this effect.
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PMID:Suppression of splenic macrophage interleukin-1 secretion following intracerebroventricular injection of interleukin-1 beta: evidence for pituitary-adrenal and sympathetic control. 164 53

Adrenocortical cell major secreted protein was purified from the conditioned medium of primary cultures of bovine adrenocortical (BAC) cells. Immunochemical analysis and N-terminal sequencing of the purified protein identified it to alpha 2-macroglobulin (alpha 2-M). It appeared that 15 out of the 17 N-terminal amino acids were conserved between adrenocortical cell major secreted protein and human alpha 2-M. Study of alpha 2-M production by BAC cells revealed that its secretion was stimulated severalfold by transforming growth factor-beta 1 (TGF-beta 1). The stimulation occurred in a time-dependent (reaching a plateau at 24 h) and dose-dependent (ED50 = 0.1 ng/ml TGF-beta 1) manner. It was blocked when BAC cells were exposed to 5,6-dichlorobenzimidazole riboside, a potent inhibitor of RNA polymerase II, suggesting that TGF-beta 1 acts as an activator of alpha 2-M gene expression at the transcriptional level. Northern blot analysis confirmed that the alpha 2-M mRNA level was increased (4-fold) in BAC cells following TGF-beta 1 treatment. TGF-beta 2, TGF-beta 1,2, basic fibroblast growth factor, and angiotensin II also appeared able to stimulate alpha 2-M secretion in BAC cells, whereas adrenocorticotropin was strongly inhibitory. Given the previous reports that TGF-beta 1 is a potent inhibitor of adrenocortical steroidogenesis (Feige J.J., Cochet, C., Rainey, W.E., Madani, C., and Chambaz, E. M. (1987) J. Biol. Chem. 262, 13491-13495) and that alpha 2-M is a TGF-beta 1-binding protein, these observations suggest that alpha 2-M may play an important role in conjunction with hormones and growth factors in the homeostatic regulation of adrenocortical functions.
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PMID:Transforming growth factor-beta stimulates the expression of alpha 2-macroglobulin by cultured bovine adrenocortical cells. 168 94

Transforming growth factor beta 1 (TGF-beta 1) has been shown previously to induce striking alterations of bovine adrenocortical cell steroidogenic functions. One of the major lesions was characterized as a loss of steroid-17 alpha-hydroxylase activity, a key step in the biosynthetic pathway leading to active corticosteroid hormones. The mechanism of this negative effect of TGF-beta 1 on adrenocortical differentiated functions was investigated. It was observed that: 1) bovine adrenocortical 17 alpha-hydroxylase activity rapidly decreased in cells exposed to TGF-beta 1, in a time (10-20 h)-dependent manner; 2) immunoblotting of the corresponding cytochrome P-450(17) alpha showed that the loss of activity was superimposable to the decrease of the cellular protein content; 3) the cell content in 17 alpha-hydroxylase messenger RNA sharply dropped under TGF-beta 1 treatment (70-75% loss within 3-4 h) as determined by Northern blot analysis; 4) TGF-beta 1 inhibited as well the induction of P-450(17) alpha normally observed under adrenocorticotropin treatment; and 5) these TGF-beta 1 effects were selectively directed toward P-450(17) alpha expression, whereas another major steroidogenic cytochrome, i.e. P-450scc, was not affected. These observations showed that TGF-beta 1 is a potent negative modulator of 17 alpha-hydroxylase expression in bovine adrenocortical cells, very possibly at the transcriptional level. TGF-beta 1 (whose gene is expressed in these cells) may thus be examined as a possible autocrine inhibitory factor implied in the regulation of adrenocortical differentiated functions, in balance with ACTH, which represents the major positive signal in this system.
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PMID:Transforming growth factor beta 1 is a negative regulator of steroid 17 alpha-hydroxylase expression in bovine adrenocortical cells. 198 28

It is likely that a complex bidirectional interaction occurs between mesangial cells and the immune cells which infiltrate the mesangium during nephritis. Macrophages and other immune cells liberate a series of mediators, including substances such as IL-1, beta-endorphin, TNF, and PDGF--all of which promote the growth of mesangial cells. The end result is mesangial cell proliferation and increased matrix production, both of which are seen in nephritis. The proliferating mesangial cells liberate autocoids such as IL-1 and PDGF, thereby setting up an amplifying loop. Simultaneously, suppressive factors such as TGF-beta are released which antagonize the actions of these growth-promoting substances. The proliferating mesangial cells also produce immunomodulatory peptides, which will in turn act on the infiltrating macrophages to stimulate their replication and activation. Such activated macrophages continue to amplify the inflammatory lesion and also promote the phagocytosis of localized antigen-antibody complexes. The net effect of all of these interactions will depend on the dominance of substances which persist and override the roles of other molecules. Studies of the controls which regulate the production of these growth factors/immune modulators will yield insights into the fundamental mechanisms which determine the outcome in glomerulonephritis.
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PMID:The biology of mesangial cells in glomerulonephritis. 223 99

Normal human cells, cells from nonmalignant proliferative lesions, and primary and metastatic tumor cells can be maintained in vitro and analyzed for requirements for growth in chemically defined media. The human melanocytic cell system with normal melanocytes, precursor nevus cells, and primary and metastatic melanoma cells has been extensively studied for the phenotypic properties of the cells, including their requirements for exogenous growth factors and other mitogens. In high calcium-containing W489 medium, normal melanocytes require four supplements: IGF-I (or insulin); bFGF, TPA, and alpha-MSH. Nevus cells are largely independent of bFGF. Depletion of TPA from medium is not as detrimental to nevus cells as it is to melanocytes, but the phorbol ester is still essential for maintenance of the typical nevic phenotype. Primary melanoma cells require at least one growth factor, IGF-I (or insulin), for continuous proliferation. On the other hand, metastatic cells of melanoma as well as of carcinomas of colon and rectum, bladder, ovary, and cervix are able to proliferate after a short adaptation period in medium depleted of any growth factors and other proteins. Doubling times of metastatic tumor cells in protein-free medium are only 30-60% longer than in FCS-containing medium. The growth autonomy of human tumor cells is apparently due to the endogenous production of growth factors. Likely candidates for autocrine growth stimulation of human tumor cells are TGF-alpha, TGF-beta, and PDGF. Melanoma and colorectal carcinoma cells express functional EGF/TGF-alpha receptors, and produce TGF-alpha, indicating that this growth factor is produced for autocrine stimulation. In addition to the use of anti-growth factor antibodies, other strategies for the inhibition of autocrine growth stimulation include mAbs to growth factor receptors, soluble receptors, receptor-mimicking antiidiotype antibodies, and active immunization against growth factors. Whether any of these therapeutic approaches is clinically feasible will need to be determined in extensive preclinical investigations.
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PMID:Growth-regulatory factors for normal, premalignant, and malignant human cells in vitro. 240 78

Type beta transforming growth factor (TGF-beta) had no detectable effect on mitogenic activities of bovine adrenocortical cells in culture. However, the presence of TGF-beta (1 ng/ml) in the medium resulted in a striking alteration of adrenocortical cell steroidogenic activities, maximally expressed after 18-20 h of treatment. TGF-treated cells exhibited a basal as well as an adrenocorticotropin-stimulated cortisol production inhibition by an average 50-60%, while cAMP accumulation in response to the hormone was not modified. Detailed study of the adrenocortical steroid biosynthetic pathway by high performance liquid chromatography analysis and supply of representative steroid substrates revealed a drastic loss (average 50%) of the steroid 17 alpha-hydroxylase activity following TGF treatment. TGF-beta thus appeared as a potent negative modulator of adrenocortical 17 alpha-hydroxylase activity. This TGF-induced loss in the activity of a key steroidogenic enzyme resulted in a shift of the adrenocortical cell secretion pattern at the expense of the 17 alpha-hydroxysteroid end products. This 17 alpha-hydroxylation alteration was also expressed when TGF-treated cells were challenged by angiotensin II. However, in this case, an additional lesion was suggested by a 70-90% inhibition in angiotensin II-activated cortisol production. This could be explained by the observation that TGF-beta exposure induced an average 50% decrease in the adrenocortical cell angiotensin II receptor number without any detectable change in receptor affinity (Ka approximately 10(9) M-1). In addition, a parallel alteration in the angiotensin II-activated phosphoinositide breakdown was observed in TGF-treated cells, indicating that TGF-beta appears as a negative effector of the adrenocortical cell transmembrane signaling system in the case of angiotensin II. It is concluded that, in vitro, TGF-beta is a potent modulator of differentiated adrenocortical cell functions, in which at least two major negatively regulated specific targets were characterized. The mechanism(s) of action and the possible physiological significance of TGF-beta in the control of the development and the differentiated functions of the adrenocortical gland in vivo remain to be established.
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PMID:Type beta transforming growth factor affects adrenocortical cell-differentiated functions. 282 Sep 72

We have shown previously that transforming growth factor beta 1 (TGF-beta 1) is antimitotic for human fetal adrenal (HFA) cells in vitro and that this effect can be partially blocked by adrenocorticotropic hormone (ACTH). In the present study, we sought to determine whether ACTH might interfere with TGF-beta 1 action by means of reducing TGF-beta 1 binding to adrenal cells. We incubated adrenal cells with 50 pM 125I-labeled TGF-beta 1 for 15 min to 3 h at 4 degree C and found that the binding of 125I-labeled TGF-beta 1 increased with time and could be inhibited in a dose-dependent manner by non-labeled TGF-beta 1 (0.05-10 nM), but not with other relevant cytokines: IL6, TNF alpha,IGF-I, IGF-II, TGF-alpha, and EGF. Pretreatment of HFA cells with ACTH (0.009-900 nM) for 4-24 h significantly increased specific 125I-labeled TGF-beta 1 binding compared to that in untreated cells; maximal increases in binding were achieved with 0.9 nM ACTH. This effect of ACTH could be mimicked by treatment of adrenal cells with dibutyryl cAMP (1 mM) or forskolin (10 microM). Scatchard analysis of data from ACTH-treated cells suggest the presence of two populations of TGF-beta 1 binding sites with different affinity and capacity of binding for the ligand.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Receptor binding of transforming growth factor-beta by human fetal adrenal cells. 766 78

Mitotically active Schwann cells isolated from adult rat sciatic nerve segments were cultivated, using a bivariate BrdU/DNA flow cytometry analysis, to test the effect of b-FGF (10 ng/ml), alpha-MSH (10 ng/ml), NGF (10 ng/ml), PDGF-AB (10 ng/ml), and TGF-beta 1 (10 ng/ml) on the cell cycle. Compared to control or cholera toxin-treated cultures, no significant differences (P < 0.05; Newmann-Keuls test) were observed in the proportion of G0G1 cells, S cells, G2M cells, and in the LI when alpha-MSH, NGF, PDGF-AB, or TGF-beta 1 were present. The S phase duration varied from 6.16 +/- 0.24 to 7.86 +/- 2.6 h, and the deduced potential doubling time was estimated at between 46.70 +/- 7.09 and 56.05 +/- 7.55 h. In contrast, when b-FGF was added to the culture, the cell cycle was significantly modified, and the proportion of G0G1 cells decreased from 68-77% to 59-64%, while the proportion of S cells increased from 14-16% to 24.0-26.4%. Although S phase duration was not significantly changed (6.02 +/- 0.36 h), the 1.7- to 2.8-fold LI increase reduced the potential doubling time to 25.99 +/- 6.13 h. We conclude from these results that only b-FGF-induced adult rat Schwann cells dramatically reenter in cell cycle and that this growth factor may be an axonally derived signal-promoting mitogenesis after nerve injury.
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PMID:Establishment of adult rat Schwann cell cultures: effect of b-FGF, alpha-MSH, NGF, PDGF, and TGF-beta on cell cycle. 792 48

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 regulatory influence of several cytokines on the expression of preproenkephalin (PPE) mRNA in human peripheral blood mononuclear cells (PBMC). By use of a quantitative reverse-transcriptase-polymerase chain reaction (RT-PCR), we demonstrate that the T helper 2 cytokines IL-4 and IL-10 are more potent in upregulating PPE mRNA expression in human PBMC than the T helper 1 cytokines IL-2 and gamma-IFN. In addition, TGF-beta is also an effective inducer of PPE mRNA. TGF-beta, IL-4 and IL-10 increase the cytoplasmatic concentration of met-enkephalin in PBMC. Secretion of met-enkephalin in the culture supernatant of IL-4- or IL-10-stimulated PBMC could not be observed, but proenkephalin A-derived met-enkephalin containing peptides could be demonstrated. IL-4 and IL-10 do not induce PPE mRNA via the same pathways. We could observe that PKA is involved in IL-4 mediated PPE mRNA induction, whereas IL-10 apparently uses another route.
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PMID:T helper 2 cytokines induce preproenkephalin mRNA expression and proenkephalin A in human peripheral blood mononuclear cells. 935 52


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