Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In studies of the regulation of hematopoiesis, increasing attention has focused on the role of bone marrow stromal cells as rich sources of various cytokines. Present studies indicate that marrow stromal cells and monocytes produce activin A, implicating this new cytokine in the paracrine control of hematopoiesis. Activin A, which was initially recognized as a beta A beta A dimeric gonadal protein, was found to potentiate the proliferation and differentiation of erythroid progenitors; both purified erythroid colony-forming units (CFU-E) and K562 cells possess high affinity receptors specific for activin A. Present studies using Western and Northern blots demonstrate the presence of beta A subunits of activin A in the conditioned medium of monocytes and stromal cells and its RNA transcripts in these cells. The presence of functional and homodimeric beta A beta A activin molecule was confirmed through bioassay with or without a blocking antiserum against activin A or an activin binding protein, follistatin; its presence is further supported by a specific enzyme-linked immunosorbent assay (ELISA) in which a monoclonal antibody reacted only with the beta A beta A dimeric form of this molecule. In other experiments, the production of activin A was found to be regulated by various cytokines and regulators. The production of activin A in monocytes was stimulated more than ninefold by treatment with granulocyte-macrophage colony-stimulating factor (GM-CSF). Activin A expression was also stimulated, albeit less potently, by bacterial lipopolysaccharide (LPS) and gamma-interferon. On the other hand, the expression of activin A in marrow stromal cells was upregulated by incubation with tumor necrosis factor-alpha (TNF-alpha), LPS, and interleukin 1 alpha (IL-1 alpha). Therefore, we propose that the local production of activin A in the microenvironment within bone marrow may fine tune the regulation of steady-state hematopoiesis. In addition, this factor may normally be produced at minimal levels, but under certain situations may be further induced to provide important biological functions.
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PMID:Regulation of production of activin A in human marrow stromal cells and monocytes. 142 3

The effect of some immunostimulants (bacterial lipopolysaccharide prodigiosan, active thymic peptide T-activin, synthetic compound levamisole) on the anti-infection resistance and metabolic function of the liver (hexobarbital sleeping-time) was studied on noninbred male mice. It was found that when administered in doses and under schedules that protected mice against lethal infection (Pseudomonas pyocyanea, i.p.) prodigiosan and levamisole inhibited metabolism of hexobarbital. T-activin was inactive in both tests. The possible mechanism of correlation is discussed.
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PMID:[The effect of stimulants of immunity on anti-infective resistance and on the activity of the liver monooxygenase system]. 236 57

Monocytes and retinal pigment epithelial cells are intimately associated in membranes of eyes with proliferative vitreoretinopathy and in certain types of uveitis. The goal of this study was to determine whether monocytes modulate cytokine expression in retinal pigment epithelial cells, and if so, to identify the monocyte products responsible for this effect. Cultured human retinal pigment epithelial cells were exposed to varying concentrations of monocyte-conditioned medium from unstimulated human monocytes for 1-48 hr, or from monocytes prestimulated with lipopolysaccharide. mRNA expression of interleukin-1 beta, interleukin-6, interleukin-8, melanoma growth stimulating activity/gro alpha and gamma, macrophage colony stimulating factor, transforming growth factor-beta 2, basic fibroblast growth factor and activin beta A chain was determined by reverse transcription polymerase chain reaction. Protein secretion of selected cytokines, interleukin-1 beta, interleukin-6, interleukin-8, macrophage colony stimulating factor and transforming growth factor-beta 2 was measured in RPE-conditioned medium by ELISA. Retinal pigment epithelial cells constitutively expressed mRNA for interleukin-6, macrophage colony stimulating factor, transforming growth factor-beta 2, basic fibroblast growth factor and activin beta A chain. Interleukin-1 beta, melanoma growth stimulating activity/gro alpha and gamma and interleukin-8 were not expressed under basal conditions. Stimulated monocyte-conditioned medium markedly induced mRNA of all cytokines except basic fibroblast growth factor and transforming growth factor-beta 2 in a dose- and time-dependent manner. Unstimulated monocyte-conditioned medium was a less potent inducing agent, but still enhanced mRNA expression of interleukin-6, interleukin-8 and melanoma growth stimulating activity/gro alpha. Stimulated monocyte-conditioned medium also induced a time-dependent increase in interleukin-6, Interleukin-8, macrophage colony stimulation factor and transforming growth factor-beta 2, but not interleukin-1 beta protein secretion (p < 0.05 for all time points). Neutralizing antibodies to interleukin-1 beta, or tumour necrosis factor alpha, but not interleukin-1 alpha, significantly reduced cytokine mRNA expression induced by stimulated monocyte-conditioned medium. The combination of all three neutralizing antibodies almost entirely eliminated monocyte-induced mRNA expression and protein production of all cytokines studied. Activated monocytes secrete a heterogeneous mixture of products that together strongly induce expression of multiple cytokines in human retinal pigment epithelial cells. Most if not all of the inducing effect can be accounted for by interleukin-1 beta and tumour necrosis factor alpha. Because cytokines have been implicated in proliferative vitreoretinopathy and uveitis, monocyte-mediated cytokine expression by RPE cells may serve to initiate and perpetuate these diseases.
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PMID:Monocyte-induced cytokine expression in cultured human retinal pigment epithelial cells. 761 19

Activin A, which was initially recognized as a gonadal protein, was implicated in the modulation of erythropoiesis through a paracrine control in the bone marrow microenvironment. Present studies demonstrate that, in contrast to T lymphocytes and cultured skin fibroblasts, human marrow stromal cells produce a functional and dimeric beta A beta A molecule (i.e., activin A). RT-PCR further indicates that both alpha and beta A mRNAs of inhibin A/activin A are produced in human stromal cells. The level of beta A subunit mRNAs, however, is in large excess over that of alpha subunit mRNAs, suggesting the predominant production of beta A beta A dimers, as well as some inhibin A (alpha beta A). It should be noted, however, that the beta A subunit can form dimeric proteins other than activin A, such as activin AB (beta A beta B) and inhibin A (alpha beta A). Hence, the presence of the beta A subunit may not necessarily indicate the production of the activin A molecule in any tissue. Therefore, a special quantitative sandwich ELISA assay specific for the dimeric beta A beta A molecule was developed for the measurement of activin A. With this assay, production of activin A in marrow stromal cells is found to be greatly enhanced by cytokines and inflammatory mediators such as TNF-alpha, IL-1 alpha, and lipopolysaccharide. These studies thus suggest that inflammatory cytokines are the inducers for activin A, probably serving a role of up-regulating activin A production locally in bone marrow microenvironment. At present, activin A is not known to play any role in inflammatory reaction; this study may thus raise the possibility that activin A performs more functions than are currently recognized. Alternatively, the enhanced production of this molecule in the bone marrow microenvironment may be regarded as a compensatory mechanism in host defenses, countering inflammatory mediators that are known to suppress erythropoiesis.
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PMID:Detection of functional and dimeric activin A in human marrow microenvironment. Implications for the modulation of erythropoiesis. 818 35

Human marrow stromal cells were analysed with immunocytochemical staining, Northern blot, and functional bioassay for production of activin A. Although Northern blot and immunocytochemical staining did not detect the alpha subunit of inhibin in human marrow stromal cells, RT-PCR analyses confirmed its presence, along with the expected activin beta A PCR products. Present studies showed that human marrow fibroblastoid cells were reactive with anti-activin A antibodies and that the production of beta A RNA was upregulated by pro-inflammatory cytokines/regulators like interleukin 1 alpha (IL-1 alpha), tumour necrosis factor-alpha (TNF-alpha), lipopolysaccharide (LPS) or 12-O-tetradecanoylphorbol 13-acetate (TPA). IL-1 alpha or TNF-alpha stimulated-marrow stromal cells accumulated beta A RNA after 2 h of incubation, reaching a peak stimulation at approximately 8 h. Biologically active activin A molecules were detected in the conditioned media by a bioassay, and their activity was specifically inhibited by a blocking antibody or an activin-binding protein, follistatin. Accumulation of bioactive activin A in conditioned medium of human marrow stromal cells increased after incubation with IL-1 alpha or TNF-alpha. Nuclear run-off assays with TNF-alpha stimulated marrow stromal cells showed that the enhanced expression of activin A was related to an increase in its rate of transcription. In contrast to the stimulatory effect of pro-inflammatory cytokines, hydrocortisone and dexamethasone at 1 x 10(-7) to 1 x 10(-6) M inhibited both the constitutive and the cytokine-stimulated expression of activin beta A RNA, and also the production of bioactive activin A protein. The upregulation of activin A production by cytokines and its suppression by glucocorticoids imply that activin A may also act as a moderator in diverse functions including host defences.
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PMID:Contrasting effects of inflammatory cytokines and glucocorticoids on the production of activin A in human marrow stromal cells and their implications. 957 69

Activins and follistatins regulate all levels of the reproductive axis, including the pituitary where they stimulate and inhibit FSH production, respectively. Gonadotropes are known to express inhibin/activin betaB and activin-B (betaBbetaB) functions as an autocrine modulator of FSH production. By contrast, the mRNA for the activin-binding protein, follistatin, is present in most pituitary cells and folliculo-stellate cells may be the major source of the protein secreted by the anterior pituitary. Interleukin-1beta (IL-1beta) is one of several cytokines known to also influence the reproductive axis. IL-1beta inhibits the hypothalamo-pituitary-gonadal (HPG) axis by suppressing GnRH and gonadal steroid production. Because several pituitary cell types, including follistatin-producing folliculo-stellate cells, are targets of IL-1beta, cytokine effects on gonadotrope function were evaluated using cultured rat anterior pituitary cells. Activin-A (0.01 to 1 nM; 24h) increased basal FSH secretion approximately 2-fold. IL-1beta (0.005 to 0.5 nM) by itself had no effect on basal FSH secretion. However, IL-1beta attenuated FSH secretion in response to all concentrations of activin-A. These results suggest that the cytokine might stimulate the local production of a factor, such as follistatin, that antagonizes the action of activin-A. RNase protection analysis indicated that IL-1beta (0.005 to 5 nM) stimulated follistatin and inhibin/activin betaB mRNA accumulation in a time-dependent manner. These in vitro effects of IL-1beta were blocked by the specific IL-1 receptor antagonist (IL-lra) and were not mimicked by either rhIL-6 or lipopolysaccharide (LPS). Treatment of intact male rats with LPS (50 microg, i.v.), which increases plasma IL-1beta and induces IL-1beta expression in many tissues, including the pituitary, produced similar time-dependent increases in pituitary follistatin and inhibin/activin subunit mRNA levels. These results suggest that IL-1beta can modulate gonadotrope responses to activins by influencing the local balance of activin-B and follistatin within the pituitary.
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PMID:Interleukin-1beta regulates pituitary follistatin and inhibin/activin betaB mRNA levels and attenuates FSH secretion in response to activin-A. 964 13

Recent evidence suggests a role for activin A, and its binding protein, follistatin, in inflammatory pathways. However, whether activin is released systemically during inflammation is not known. In this study, a release of activin A into the circulation occurred in sheep within 1 hour of injection of lipopolysaccharide. This rapid peak in activin A preceded the release of the key inflammatory cytokines, tumor necrosis factor-alpha and interleukin-6. Follistatin release into the circulation occurred some 4 hours after the peak of activin A and continued out to 24 hours from lipopolysaccharide treatment. These data are the first to document a circulatory response of activin A to an inflammatory stimulus, and together with previous findings, suggest that activin A may have both pro- and anti-inflammatory actions in regulating cytokine-driven pathways.
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PMID:Activin A release into the circulation is an early event in systemic inflammation and precedes the release of follistatin. 1080 3

Using a combination of polymerase chain reaction (PCR) procedures, we have cloned and sequenced the rat activin beta(E) subunit cDNA. The putative protein corresponding to the prepro-activin beta(E) subunit was predicted to comprise 350 amino acids which, when cleaved between amino acid residues 236 and 237, would yield a mature polypeptide of approximately M(r) 12 500 with a predicted pI of 5.1. Two cDNA transcripts for activin beta(E) were identified; these differed by 738 bp in the 3'-untranslated region. Activin beta(E) mRNA transcripts were expressed only in rat liver and lung tissue as assessed by Northern blotting and PCR analysis. Relatively higher levels of both transcripts were found in the liver, whereas the lung contained lower levels that were detectable by PCR only. In situ hybridisation data showed that, within the liver, activin beta(E) mRNA was localised to hepatocytes. In vivo treatment with lipopolysaccharide as a means of activating the immune system and the hepatic acute-phase response resulted in stimulated activin beta(E) mRNA levels, compared with untreated, control rats. This increased expression was accompanied by a preferential increase in the amount of the long activin beta(E) transcript over the shorter transcript. These findings suggested that the two activin beta(E) mRNA transcripts may be products of alternative splicing events or use alternative polyadenylation sites which are differentially regulated during inflammation. These data provide evidence of a role for activin beta(E) in liver function and inflammation in the rat.
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PMID:Cloning and regulation of the rat activin betaE subunit. 1082 34

Inhibin, activin, and transforming growth factor beta (TGFbeta) inhibited lipopolysaccharide (LPS)-induced lymphocyte proliferation in a dose-dependent fashion. These induced suppressions were neutralized by coincubation of a preparation of antibodies to inhibin and TGFbeta, respectively. Inhibin and activin also facilitated TGFbeta-mediated immunosuppression of LPS-induced proliferation of splenocytes. These gonadal proteins showed no effect on phytohemagglutinin- or concanavalin A (Con-A)-induced proliferation of lymphocytes. However, inhibin facilitated and activin inhibited the TGFbeta-mediated immunosuppression in thymocytes stimulated by Con-A. These findings suggest that inhibin or activin by itself, and/or together with TGFbeta, may play an important role in immune response. Copyright 1995 S. Karger AG, Basel
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PMID:Inhibin and Activin Modulate Transforming Growth Factor-beta-Induced Immunosuppression. 1172 59

Folliculostellate cells of the anterior pituitary are postulated to be an important source of factors, such as follistatin, that regulate pituitary function by intercellular communication. To gain further insight into the function of this cell type, folliculostellate cells were enriched from cultured rat anterior pituitary cells, and an immortalized cell line designated FS/D1h was established and characterized. These FS/D1h cells express S100 immunoreactivity and produce IL-6 but not pituitary hormones such as GH, ACTH, FSH, and LH. Importantly, FS/D1h cells express large amounts of follistatin mRNA and secrete the protein, as quantified indirectly by the amount of [(125)I]activin A immunoprecipitated with a follistatin antiserum. The FS/D1h cells also express alpha, betaA, and betaB inhibin/activin subunit mRNAs, but whether they produce the corresponding activins and inhibins has not been determined. The response of FS/D1h cells to agents thought to modulate folliculostellate cell function was evaluated. IL-1beta (0.005-5 nM) stimulated the secretion of follistatin and increased mRNA expression. In parallel, IL-6 secretion was stimulated. Dexamethasone, pituitary adenylate cyclase-activating polypeptide(1-27), and lipopolysaccharide but not testosterone, 12-O-tetradecanoylphorbol-13-acetate, or forskolin also increased follistatin secretion. Surprisingly, activin had no effect on follistatin mRNA levels, despite the fact that FS/D1h cells express ActRII, ActRIIB, and ALK-4 (ActRIB). Activin, on the other hand, induced Smad7 mRNA accumulation and exerted an antiproliferative effect on FS/D1h cells. Altogether, these observations support the possibility that follistatin originating from folliculostellate cells participates in mediating the effects of IL-1beta, glucocorticoids, and other agents on the response of pituitary cells to activins.
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PMID:Rat anterior pituitary folliculostellate cells are targets of interleukin-1beta and a major source of intrapituitary follistatin. 1253 36


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