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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A small portion of human lung mononuclear cells are very potent stimulators of allogeneic resting T cells. Although several-fold more effective than phagocytic alveolar macrophages (AM) and blood monocytes (Mo), they do not produce more of the lymphocyte co-stimulators interleukin-1-alpha (IL-1 alpha), interleukin-1-beta (IL-1 beta), or tumor necrosis factor-alpha (TNF-alpha) than did Mo. Blocking antibodies against IL-1 alpha, IL-1 beta, TNF-alpha, and IL-6 did not reduce T cell proliferation. These potent antigen-presenting cells (APC) are loosely adherent and do not have phagocytic inclusions. Most of them have the marker RFD1 of dendritic cells (DC) rarely present on Mo or AM and have a strong tendency to form clusters with T cells like murine DC. Thus, we demonstrate an example in the human system of a dissociation between T cell activation and IL-1 or TNF-alpha production by DC or Mo, implying a major role for other "co-stimulating signals" by lung APC with dendritic features. The presence of different APC with various co-stimulating signals may be of importance for T cell subsets modulation.
Am J Respir Cell Mol Biol 1990 Jun
PMID:Dissociation between allogeneic T cell stimulation and interleukin-1 or tumor necrosis factor production by human lung dendritic cells. 234 59

The interleukin 1 (IL-1) family of proteins has a central role in modulating immune and inflammatory responses. Two major IL-1 proteins, designated alpha (IL-1 alpha) and beta (IL-1 beta), are produced by activated macrophages and other cell types. In an effort to understand the similarities and differences in the physicochemical and functional properties of these two proteins, a program was initiated to determine their structures. Crystals of IL-1 alpha were grown, and the three-dimensional structure at 2.7-A resolution was solved. The technique of multiple-wavelength anomalous dispersion (MAD) with the selenomethionine form of IL-1 alpha was utilized in combination with a single mercury derivative to provide the starting phases. Partial refinement of the IL-1 alpha model has been performed as well. The overall structure is composed of 14 beta-strands and a 3(10) helix. The core of this structure is a capped beta-barrell that possesses 3-fold symmetry and displays a topology similar to that observed for IL-1 beta [Priestle, J. P., et al. (1988) EMBO J. 7, 339-343] and soybean trypsin inhibitor (STI) [McLachlan, A. D. (1979) J. Mol. Biol. 133, 557-563]. In this paper, the overall structure of IL-1 alpha and the nature and fidelity of the internal 3-fold symmetry are discussed. Comparisons with IL-1 beta and STI are made within these contexts.
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PMID:Structure of interleukin 1 alpha at 2.7-A resolution. 234 41

We determined whether normal human lung fibroblasts expressed cell-associated thymocyte-stimulating activity in response to recombinant interleukin-1 (rIL-1) (alpha and beta) and recombinant tumor necrosis factor (rTNF). Individually, rIL-1 and rTNF induced fibroblast expression of thymocyte-stimulating activity, with rIL-1 being significantly more potent. Importantly, combining rIL-1 and rTNF resulted in a synergistic increase in fibroblast thymocyte-stimulating activity. This synergistic interaction was dose dependent for both cytokines and was not noted when gamma-interferon was combined with rIL-1 or rTNF. In all cases, the thymocyte-stimulating activity was the result of an IL-1 alpha-like moiety whose maximal production required protein synthesis. IL-1 alpha activity could be detected after as little as 4 h, peaked after 24 h, and returned toward normal with longer periods of cytokine-fibroblast incubation. However, cytokine-stimulated fibroblasts that no longer expressed IL-1 alpha activity could be induced to re-express this activity with repeat cytokine challenge. Induction of fibroblast IL-1 alpha by IL-1 and/or TNF may be an important mechanism amplifying IL-1-mediated biologic events at sites of local inflammation.
Am J Respir Cell Mol Biol 1990 Jul
PMID:Interleukin-1 and tumor necrosis factor synergistically stimulate lung fibroblast interleukin-1 alpha production. 236 34

The rat alpha 1-acid glycoprotein (AGP) gene is transcriptionally regulated by dexamethasone, interleukin 1 (IL-1), hepatocyte-stimulating factor, and beta 2 interferon. The steroid and peptide hormones stimulate expression of the AGP gene synergistically as well as independently. The regulatory sequence responsible for dexamethasone-stimulated expression has been localized previously to a region that is 120 to 64 base pairs (bp) upstream of the transcription start site (H. Baumann and L. E. Maquat, Mol. Cell. Biol. 6:2551-2561, 1986). To identify the regulatory sequence that is responsive to the peptide hormones, different lengths of the AGP gene 5'-flanking DNA were linked to the chloramphenicol acetyltransferase gene and then assayed for hormone-inducible chloramphenicol acetyltransferase gene expression in transiently transfected HepG2 cells. We demonstrate that an enhancer region that is responsive to IL-1, hepatocyte-stimulating factor, and beta 2 interferon lies within a 142-bp sequence located 5,300 to 5,150 bp upstream of the transcription start site. This distal regulatory region can confer hormone inducibility to a heterologous promoter; exert its affect in either orientation; and function, to a lesser degree, in nonhepatic but IL-1-responsive cells.
Mol Cell Biol 1988 Jan
PMID:Hepatocyte-stimulating factor, beta 2 interferon, and interleukin-1 enhance expression of the rat alpha 1-acid glycoprotein gene via a distal upstream regulatory region. 244 85

Human alveolar macrophages (AM) were obtained by bronchoalveolar lavage from healthy donors, and their abilities to produce extracellular and cell-associated interleukin 1 (IL-1) in response to various activation stimuli were compared with those of autologous blood monocytes. The production of IL-1 alpha and IL-1 beta by monocytes and AM was examined by thymocyte co-stimulation assay and enzyme immunoassays (EIA). Results showed that when activated with lipopolysaccharide (LPS) or desmethyl muramyl dipeptide (norMDP), AM released much less extracellular IL-1 beta than did blood monocytes. In contrast, these activated AM produced more cell-associated IL-1 than did blood monocytes. When the IL-1 activity was examined by the thymocyte assay, the extracellular and cell-associated IL-1 produced by the two cell types were largely IL-1 beta and IL-1 alpha, respectively, as shown by antibody neutralization. The cell-associated IL-1 activity of AM induced by the synergistic actions of suboptimal concentrations of recombinant interferon-gamma (rIFN-gamma) and norMDP was also higher than that of autologous blood monocytes. Consistent with these findings on AM, macrophages generated in vitro by maturation of blood monocytes produced higher levels of cell-associated IL-1 activity than did freshly isolated monocytes. These observations suggest that AM may play a critical role in situ regulation of pulmonary inflammatory and immune reactions through production of cell-associated IL-1 alpha.
Am J Respir Cell Mol Biol 1989 Dec
PMID:Normal human alveolar macrophages have more ability than blood monocytes to produce cell-associated interleukin-1-alpha. 248 61

The serine protease complement factor B (Bf), an acute phase plasma protein, is a component of the alternative pathway of complement activation. Previous studies revealed that several cytokines including IFN-gamma and IL-1 are involved in mediating acute phase Bf expression. To determine the molecular details of Bf expression we isolated, sequenced and characterized the 5' flanking regions of the human and murine Bf genes. In both species the Bf transcriptional start site in liver was located less than 400 bp 3' to the polyadenylation site of the upstream C2 gene. This upstream intergenic region contained greater than 65% nucleotide homology between species. Within this region, an IRS and three heat shock consensus elements were found in the murine sequence in an identical position to that of the human. To examine the functional details of Bf expression, a series of mouse and human Bf promoter-chloramphenicol acetyltransferase (CAT) chimeric gene constructs were transfected into mouse L or human HepG2 cells. Analysis of expression of these fusion gene constructs revealed that 1) cis-acting DNA sequences identified, at least in part, in the 3' untranslated region of the C2 gene (within the 400 bp upstream of the Bf cap site) mediate responsiveness to IL-1 and IFN-gamma, 2) the responsiveness to each mediator appears to be conferred by separate upstream regions similar in position and homologous in man and mouse, and 3) the IL-1 responsive region in both species appears to have the characteristics of an enhancer element. The results of this analysis suggest a selective pressure to conserve the intergenic sequence between C2 and Bf genes and that further studies of these sequences will be useful in elucidating mechanisms controlling the acute phase response.
Mol Cell Biochem 1989 Aug 15
PMID:Regulation of human and murine complement: comparison of 5' structural and functional elements regulating human and murine complement factor B gene expression. 250 33

The fungicidal and bactericidal activities of human alveolar macrophages (AM) and peripheral blood monocytes (PBM) from 18 healthy volunteers were evaluated. The results showed that AM were able to phagocytize and kill Candida albicans, Pseudomonas aeruginosa, and Staphylococcus aureus. However, killing of the bacteria was already complete in 2 h, whereas killing of Candida required 4 to 6 h despite an early phagocytosis of yeast cells. The fungicidal activity of freshly collected AM and PBM was also tested after effector cell exposure to interferon-gamma (IFN-gamma), interleukin-1-alpha (IL-1 alpha), endotoxin lipopolysaccharide (LPS), or interleukin 2 (IL-2). It was found that treatment with IFN-gamma, IL-1 alpha, or LPS significantly augmented macrophage and PBM candidacidal activity, whereas the addition of IL-2 was ineffective. We also evaluated killing of C. albicans by AM cultured in vitro for different times. While phagocytosis was apparently unaffected, the candidacidal activity progressively decreased over the in vitro culture period, an effect that was largely reversed by cell exposure to IFN-gamma, IL-1 alpha, or LPS. In an experimental model in which mice infected with an agerminative C. albicans strain (PCA-2) resisted lethal microbial challenge, freshly harvested AM showed increased cytotoxic activity to Aspergillus fumigatus in vitro as well as enhanced IL-1 production. In conclusion, present data confirm the crucial role of AM in the surveillance of bacterial and fungal infections and indicate that treatment of these cells with IFN-gamma or IL-1 alpha is able to enhance their antimicrobial capability.
Am J Respir Cell Mol Biol 1989 Jul
PMID:Modulation of anti-Candida activity of human alveolar macrophages by interferon-gamma or interleukin-1-alpha. 251 51

Human endothelial cells have been shown to be distinctive from other IL-1 responsive cells (e.g. murine thymocytes), in the equal units of murine and human IL-1 do not have the same endothelial cell stimulatory effect, as measured by increased lymphocyte adherence. In this paper, the cell surface IL-1 receptors of human endothelial cells, fibroblasts and T-lymphocytes have been compared, to investigate whether endothelial cells have a unique receptor for IL-1. IL-1 receptors were isolated by both immunoprecipitation and chemical cross-linking to the ligand. Both techniques demonstrated that human endothelial cells are similar to human T-lymphocytes and fibroblasts, in that they all have a 78,000 mol. wt IL-1 receptor.
Mol Immunol 1989 Mar
PMID:The molecular weight of the endothelial cell IL-1 receptor is 78,000. 252 20

Human alveolar macrophages release in vitro a factor that inhibits both random migration and chemotaxis of human polymorphonuclear neutrophils (PMN). This factor is not cytotoxic and is recovered in culture supernatants of alveolar cells from most nonsmoking normal subjects. The inhibitor can be detected 30 min after cell cultures are established and is still produced after 24 h in culture. Its release was inhibited by cycloheximide. When supernatants are separated by molecular sieving (I-60 Waters HPLC column), most of the inhibitory activity is recovered in the low-molecular-weight fractions of the chromatogram (less than 1,000 D). The inhibitor has a broad spectrum of activity against known chemoattractants in that it reduces significantly the chemotaxis of PMN induced by the formyl peptide FMLP, by the complement fragment C5a, and by leukotriene B4; it also decreases the chemotactic activity associated with a monocyte-derived interleukin 1 preparation and the chemotactic activity derived from alveolar macrophage culture supernatants. The inhibitory factor is partially heat labile, is sensitive to aminopeptidase M, and is nonpolar. Both phorbol myristate acetate (PMA) and FMLP-induced superoxide release by PMN are diminished significantly in the presence of this inhibitory factor (p less than 0.01 for PMA and p less than 0.05 for FMLP). The inhibitor also reduces monocyte chemotaxis but has no effect on monocyte random migration. Finally, studies with [3H]FMLP indicate that this inhibitor does not act at the site of receptor binding on PMN. Thus, human alveolar macrophages can release in vitro both neutrophil chemotactic factors and an apparent neutrophil-inhibiting factor that may modulate positively and negatively the movement and the respiratory burst of neutrophils in the alveolar space.
Am J Respir Cell Mol Biol 1989 Nov
PMID:Human alveolar macrophages release a factor that inhibits phagocyte function. 256 89

The formation of CD8+ killer cells from nonlytic thymocyte precursors is mediated by interleukin 2 and a cytokine termed CTL differentiation factor (CDF). While several reports have focused on the effects of recombinant molecules on the development of CTL, the natural protein responsible for CTL development that is produced by normal leukocytes has not been conclusively identified. A 24 kD native protein with CDF activity was enriched from leukocyte conditioned medium and neutralizing antibodies were produced. Utilizing immunoaffinity chromatography and reverse phase chromatography, we purified this CDF to homogeneity. All 21 amino acid residues at the NH2-terminus of CDF were found to be identical to that of IL-6. Natural CDF and IL-6 share many of the same biological properties, including costimulation of thymocyte proliferation with IL-1. Antibodies against CDF or IL-6 can block the activity of either cytokine, and anti-CDF blocks the activity of bulk leukocyte conditioned medium. These results indicate that IL-6 is the principal CTL differentiation factor produced by stimulated human leukocytes.
J Mol Cell Immunol 1989
PMID:Interleukin 6 is the principal cytolytic T lymphocyte differentiation factor for thymocytes in human leukocyte conditioned medium. 261 Aug 54


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