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Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Transforming growth factor (TGF)-beta and interleukin (IL)-10 inhibited lipopolysaccharide (LPS)-induced macrophage production of the inflammatory cytokines tumor necrosis factor-alpha (TNF), IL-1 alpha, and IL-1 beta by contrasting post-transcriptional mechanisms. TGF-beta acted slowly and late, as it required 12-16 h to exert a suppressive effect, and inhibited TNF production even when added 6 h after LPS. TGF-beta affected neither the level of TNF mRNA, the release of preformed TNF nor the degradation of TNF. Thus, TGF-beta appeared to inhibit translation of TNF mRNA. IL-10 not only suppressed TNF release to a 25-fold greater extent than TGF-beta, but also inhibited release of IL-1. In contrast to TGF-beta, IL-10 acted on an early step in cytokine production, its effect being maximal 3 h after addition of LPS. Unlike TGF-beta, IL-10 markedly suppressed TNF, IL-1 alpha, and IL-1 beta mRNA levels. However, this was accomplished without suppressing transcription of the corresponding genes. Moreover, cycloheximide antagonized the IL-10-dependent reduction in cytokine mRNA levels. Thus, IL-10 may induce a ribonuclease active on cytokine transcripts or may induce a protein that enhances the susceptibility of TNF, IL-1 alpha, and IL-1 beta mRNAs to ribonucleolytic action. We conclude that IL-10 and TGF-beta induce different phenotypes of macrophage deactivation, and deactivate macrophages by different mechanisms: IL-10 promotes degradation of cytokine mRNA, while TGF-beta primarily suppresses translation.
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PMID:Contrasting mechanisms for suppression of macrophage cytokine release by transforming growth factor-beta and interleukin-10. 142 77

The effects of lipopolysaccharide (LPS), recombinant human tumor necrosis factor-alpha (TNF), recombinant human interleukin 1-beta (IL-1 beta), and interferon-gamma (IFN-gamma) on IL-6 production were determined by enzyme-linked immunosorbent assay (ELISA) and by Northern blot analysis in cultured human dermal microvascular endothelial cells (HDMEC). Unstimulated HDMEC did not produce significant amounts of IL-6, whereas lipopolysaccharide (LPS), TNF, and IL-1 beta were potent inducers of HDMEC-derived IL-6 production. Treatment with IFN-gamma had no effect. IL-1 beta stimulation resulted in pronounced IL-6 production after 4 h, followed by complete downregulation at the transcriptional level after 24 h. In contrast, LPS and TNF induced prolonged stimulation of IL-6 production by HDMEC as IL-6 mRNA transcripts were still detected after 24 h treatment and IL-6 protein was markedly increased at this timepoint. The effects of hydrocortisone, dexamethasone, calcitriol, acitretin, and cyclosporin A on TNF- or IL-1 beta-induced IL-6 production by HDMEC were determined by ELISA. Both hydrocortisone and dexamethasone dose-dependently inhibited the cytokine-induced IL-6 production, whereas the inhibition by calcitriol was less pronounced. In contrast, acitretin and cyclosporine A had no influence on cytokine-induced HDMEC IL-6 production. These results disclose dermal endothelial cells as a major source for the pro-inflammatory cytokine IL-6, involved in the regulation of inflammatory skin processes. As IL-6 seems to play a key role in the pathogenesis of psoriasis, the beneficial effects of corticosteroids and calcitriol in this disease may partly be explained by their ability to inhibit HDMEC-derived IL-6 production.
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PMID:Cytokine-stimulated human dermal microvascular endothelial cells produce interleukin 6--inhibition by hydrocortisone, dexamethasone, and calcitriol. 143 Dec 12

The presence of chronic inflammatory cells in the adventitia and media of abdominal aortic aneurysms and aortic occlusive disease suggest an immunologic response. The purpose of this study is to determine whether normal or diseased infrarenal aortas liberate the inflammatory cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta). Twenty-six infrarenal aortic biopsies (5 aortic occlusive disease, 15 abdominal aortic aneurysms, and 6 cadaveric donors) were weighed, minced into small pieces, and incubated in media for 48 hours. Conditioned media was harvested at 48 hours and assayed for IL-1 beta or TNF-alpha with use of an ELISA assay. Comparison of groups was performed with a one-way analysis of variance. The constitutive IL-1 beta produced by abdominal aortic aneurysms was significantly different than that in cadaveric donors (908 +/- 194 pg/ml [SE] vs 100 +2- 30 pg/ml). There was no statistically significant difference between abdominal aortic aneurysms and aortic occlusive disease (908 +/- 194 pg/ml vs 604 +/- 256 pg/ml) or aortic occlusive disease and cadaveric donor (604 +/- 256 vs 100 +/- 30). In time-course studies for the release of IL-1 beta, abdominal aortic aneurysms demonstrated maximal release at 48 hours. IL-1 beta release was augmented by lipopolysaccharide in all categories. A dose response curve demonstrated maximal IL-1 beta release on stimulation with 5 micrograms/ml LPS. Constitutive TNF-alpha production was low, ranging from 13 +/- 1.5 pg/ml in cadaveric donor, to 20 pg/ml in aortic occlusive disease, and 24 +/- 11 pg/ml in abdominal aortic aneurysms. There was no augmentation in TNF-alpha with lipopolysaccharide.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Interleukin-1 beta and tumor necrosis factor-alpha release in normal and diseased human infrarenal aortas. 143 67

In this study we examined the effects of preincubation with aflatoxin B1 (AFB1) on the ability of bovine monocytes to produce the immunological mediator interleukin-1 (IL-1). Monocytes preincubated for 6-24 h with 10 micrograms ml-1 AFB1 demonstrated a diminished capacity to release IL-1 activity in response to bacterial lipopolysaccharide (LPS). Preincubation for less time, or with lower concentrations of AFB1, did not affect IL-1 release. Pretreatment of monocytes with AFB1 also resulted in diminished release of IL-1 activity in response to in vitro infection with Listeria monocytogenes. Incubation with AFB1 reduced the amount of IL-1 beta mRNA in LPS-stimulated bovine monocytes; however, this was observed only at high concentrations of AFB1 that non-specifically reduced steady-state transcription of actin mRNA. We therefore concluded that AFB1 does not specifically suppress monocyte release of IL-1, other than through its general inhibition of mRNA transcription.
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PMID:Effect of aflatoxin B1 on in vitro production of interleukin-1 by bovine mononuclear phagocytes. 144 Dec 24

Following the observation that interleukin 1 beta (IL-1 beta) production in lipopolysaccharide (LPS)activated monocytes increases in concert with a rise in intracellular pH (pHi), the role of ion transport in IL-1 beta production was investigated. The amiloride analogue 5-(N-ethyl-N-isopropyl)amiloride (EIPA), an inhibitor of the Na(+)-H+ antiporter, inhibited extracellular IL-1 beta. The replacement of Na+ in the culture medium with sucrose or choline chloride also prevented monocyte activation. The sodium ionophore monensin, in doses from 100 pM to 1 microM, potentiated LPS-stimulated extracellular IL-1 beta when compared with LPS alone. In the absence of LPS activation, monensin by itself at 10 nM stimulated IL-1 beta production to 63%. EIPA at 10 microM inhibited the Na+ influx, the rise in pHi, and intra- and extracellular IL-1 beta production in activated monocytes; this inhibition was reversed by 10 nM monensin. In the absence of bicarbonate, or in the presence of 10 microM 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid, the pHi of activated monocytes and the total protein synthesis did not change, but the production of IL-1 beta was inhibited. The data suggest that the stimulated influx of Na+ via the Na(+)-H+ antiporter regulates both pHi and IL-1 beta production in LPS-activated monocytes. The requirement for bicarbonate indicates an additional mechanism(s), separate from the modulation of pHi and intracellular Na+.
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PMID:Effects of intracellular ions on interleukin-1 beta production by lipopolysaccharide-activated human monocytes. 144

Monocyte recruitment is essential for maintenance of normal pulmonary macrophage populations. In addition, acute and chronic inflammatory pulmonary diseases are associated with sequestration of mononuclear phagocytes in the lung. Although alveolar macrophages (AM phi) can secrete a number of potent inflammatory and chemoattractment mediators, these immune cells do not produce monocyte chemotactic peptide (MCP-1) in response to lipopolysaccharide (LPS), tumor necrosis factor (TNF), or interleukin-1 beta (IL-1 beta). The pulmonary fibroblast (PF) may play a pivotal role in monocyte recruitment. In these studies, we demonstrate a time- and dose-dependent production of PF-derived steady-state MCP-1 mRNA, MCP-1 antigen, and monocyte chemotactic bioactivity attributable to MCP-1. In cellular models examining cytokine networks between AM phi and PF, LSP-stimulated AM phi (conditioned media) induced PF-derived steady-state MCP-1 mRNA expression that was markedly attenuated by the presence of neutralizing TNF and IL-1 beta antibodies. Furthermore, we showed the dose- and time-dependent suppression of IL-1 beta-stimulated PF-derived MCP-1 by dexamethasone and prostaglandin E2. These findings demonstrated that PF are an important cellular source of MCP-1 and this production of MCP-1 may be influenced by immunomodulators.
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PMID:Expression and regulation of human pulmonary fibroblast-derived monocyte chemotactic peptide-1. 144 57

The effect of tumor necrosis factor-alpha (TNF-alpha) on the febrile response to interleukin-1 beta (IL-1 beta) was investigated in rats. While both of these substances are capable of causing fever when injected into rats, an earlier study showed that the injection of antiserum against TNF-alpha enhanced endotoxin [lipopolysaccharide (LPS)] fever, suggesting that physiological levels of circulating TNF may act to limit the magnitude of fever. In the present study, the intraperitoneal injection of 1 microgram/kg of TNF-alpha significantly attenuated the fever due to the intraperitoneal injection of 10 micrograms/kg of IL-1 beta. Higher doses of TNF-alpha (10 and 50 micrograms/kg injected ip) slightly lowered the febrile response to this dose of IL-1 beta, but these changes were not significant. None of these doses of TNF-alpha alone significantly altered body temperature. The injection of 1 microgram/kg of TNF-alpha also significantly lowered the febrile response to the intraperitoneal injection of 10 micrograms/kg of LPS. The febrile responses to the preoptic area (POA) or intraperitoneal injection of IL-1 beta were not changed when a nonpyrogenic dose of TNF-alpha was simultaneously injected into the POA. Further studies are needed, however, before we can conclude that TNF does not act in the central nervous system to control the febrile response. These data support the hypothesis that nonpyrogenic levels of TNF act in the systemic circulation to suppress the development of fever.
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PMID:Systemic injection of TNF-alpha attenuates fever due to IL-1 beta and LPS in rats. 144 36

1 alpha, 25-Dihydroxyvitamin D3 (D3) (100 nM) and interferon-gamma (IFN-gamma) (100 U/ml) cooperatively inhibited the proliferation of HL-60 cells, and synergistically induced their monocytic differentiation. The growth-promoting effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) (10 ng/ml) was inhibited appreciably by D3 and slightly by IFN-gamma. Despite the clear difference in their effects on growth of HL-60 cells, both IFN-gamma and GM-CSF in combination with D3 induced cell cycle changes, decreasing the number of cells in the S phase and increasing their percentage in the G1/0 phase. GM-CSF alone had no effect on differentiation, but enhanced differentiation induced by D3 distinctly though to a limited extent, and also enhanced monocytic differentiation, including morphological changes of HL-60 cells in the presence of D3 and IFN-gamma. GM-CSF as well as D3 and IFN-gamma induced interleukin-1 beta (IL-1 beta) production by the HL-60 cells, clearly indicating their importance in differentiation of these cells. IFN-gamma and GM-CSF had mutually potentiating effects and induced maximum IL-1 beta production in response to lipopolysaccharide (LPS) in the presence of D3. Thus despite its growth-promoting effect, GM-CSF is a potential inducer of monocytic differentiation of human myeloid leukemia cells, because in cooperation with IFN-gamma it induced monocyte-macrophage differentiation of HL-60 cells in the presence of D3.
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PMID:The role of granulocyte-macrophage colony-stimulating factor in induction of monocytic differentiation of HL-60 cells: synergistic interaction with 1 alpha, 25-dihydroxyvitamin D3 and interferon-gamma in inducing interleukin-1 beta. 144 89

Serum levels of various cytokines, tumor necrosis factor-alpha (TNF-alpha), interleukin 1-beta (IL1-beta), and interleukin 2 (IL2), and of soluble IL2 receptors (sIL2R) were determined in 30 patients with definite systemic sclerosis (SSc). Spontaneous and lipopolysaccharide-or mitogen-induced production of the cytokines, TNF-alpha, IL1-beta, and IFN-gamma, by peripheral blood mononuclear cells (PBMNC) of these SSc patients was measured by immunoassays. The patients were divided into three groups: 12 with limited cutaneous disease (lcSSc), 7 with diffuse cutaneous disease (dcSSc) < 3 years duration, and 11 with dcSSc > 3 years duration. None were treated with cytotoxic drugs or biologic response modifiers. Sera of patients with SSc had elevated sIL2R levels, and only low levels of IL2 (1-2 U/ml) were detected in 10/29 sera tested. Spontaneous production of TNF-alpha and IL1-beta by PBMNC of patients with SSc (829 pg/ml +/- 215 SEM and 728 pg/ml +/- 186, respectively) was significantly higher than that by normal PBMNC obtained from 30 volunteers (25 +/- 10 and 34 +/- 6 pg/ml, respectively) and tested at the same time as patients' PBMNC. The largest increases in spontaneous release of TNF-alpha or IL1-beta were seen in patients with early dcSSc. No significant difference in spontaneous IFN-gamma production by patient or control PBMNC was detected. On the other hand, the mean level of mitogen-induced IFN-gamma production by PBMNC was significantly depressed in patients with SSc (103 U/ml +/- 18 vs 255 +/- 33 U/ml in controls). In vitro-induced production of TNF-alpha or IL1-beta by patients' PBMNC was comparable to that of normal PBMNC. These data indicate that in vivo-activated PBMNC of patients with SSc spontaneously secrete excessive amounts of fibrogenic cytokines, which are involved in modulation of connective tissue synthesis.
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PMID:Cytokine production and serum levels in systemic sclerosis. 145 30

The results reported here indicate that activated species of Hageman factor (HF, factor XII), a protein that mediates blood clotting, fibrinolysis, and activation of the complement cascade, induce elaboration of interleukin 1 (IL-1) by human monocytes. Augmentation of IL-1 production in mononuclear cell cultures was observed when HF was present along with lipopolysaccharide (LPS) but was not observed with HF alone. Furthermore, antiserum to HF abrogated the enhancement of IL-1 in cultures containing HF and LPS. Total IL-1 activity, which represents secreted and cell-associated IL-1, was enhanced in LPS-stimulated mononuclear cultures by HF. In the absence of LPS, the initial activation product of HF, HFa, which contains the serine protease enzyme activity and the surface-binding domains of the protein, induced IL-1 beta protein and mRNA. In the presence of LPS, the enzymatic moiety (HFf), which is also contained in HF and HFa, amplified IL-1 production. Induction and amplification of monocyte IL-1 by HF provides further evidence for establishing a role for HF in the acute-phase reaction and the cellular immune response.
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PMID:Induction of expression of monocyte interleukin 1 by Hageman factor (factor XII). 146 26


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