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

We investigated the effects of silica (SiO2) and titanium dioxide (TiO2) on the pulmonary recruitment of inflammatory cells and the ability of alveolar macrophages (AMs) to release the pro-inflammatory cytokines, interleukin 1 (IL-1) and tumor necrosis factor alpha (TNF). Rats were intratracheally instilled with 5 to 100 mg/kg of the materials, and bronchoalveolar lavage cell populations and AM cytokine release were characterized on days 1, 7, 14, and 28. Both dusts elicited dose-related increases in neutrophils, lymphocytes, and AMs; however, this response was more pronounced and persistent with SiO2. SiO2 at greater than or equal to 50 mg/kg increased AM release of IL-1 and TNF at all time points; lower SiO2 doses had either a transient or no effect on AM-derived cytokines. TiO2 did not result in AM IL-1 release and increased TNF release transiently at doses greater than or equal to 50 mg/kg. Both dusts primed AMs to release increased levels of IL-1 and TNF upon in vitro stimulation with lipopolysaccharide. Histopathology (day 28) demonstrated dose-related interstitial inflammation associated with SiO2 exposure, an effect that was less severe with TiO2. SiO2 doses of greater than or equal to 50 mg/kg elicited a granulomatous response. Development of granulomatous inflammation only at SiO2 doses for which persistent AM IL-1 release occurred suggests involvement of this cytokine in the formation of SiO2-induced granulomas. The ability of SiO2 to activate AM release of IL-1 and TNF in a more pronounced and persistent manner than TiO2 is likely responsible, at least in part, for the greater inflammation and pneumotoxicity associated with SiO2.
Am J Respir Cell Mol Biol 1990 Apr
PMID:Pulmonary response to silica or titanium dioxide: inflammatory cells, alveolar macrophage-derived cytokines, and histopathology. 215 74

A system which allows direct selection for curing of plasmids in Gram-negative bacteria was used to generate derivatives of Rhizobium leguminosarum VF39 cured of each of six plasmids present in this strain. Phenotypes could be correlated with the absence of five of the six plasmids. The smallest plasmid, pRleVF39a, carries genes for the production of a melanin-like pigment as has been previously reported. Plasmid pRleVF39d carries nodulation and nitrogen fixation genes. Curing of the plasmids pRleVF39c and pRleVF39e gave rise to strains which formed Fix- nodules on peas, lentils, and faba beans. The nodules formed by the strains cured of pRleVF39c contained few, if any, bacteria. Analysis of washed cells by SDS-PAGE showed that this strain is defective in lipopolysaccharide (LPS) production; the defect could be complemented by introducing plasmids from several other R. leguminosarum strains, and by the R. leguminosarum biovar phaseoli LPS gene clones pCos126 and pDel27. The nodules formed by the strain cured of pRleVF39e had a reduced symbiotic zone, an enlarged senescence zone, and an abundance of starch granules. This strain grew at a much slower rate than the wild type, was unable to grow on minimal medium, and no longer produced melanin. These defects could be complemented by at least one other Rhizobium plasmid, pRle336e, a plasmid of strain 336 which is distinct from the nodulation plasmid (pRle336c) and the plasmid (pRle336d) which could complement the LPS defect associated with the loss of pRleVF39c. This demonstrates that genes necessary for symbiosis can be carried on at least three different plasmids in R. leguminosarum.
Mol Microbiol 1990 Apr
PMID:Two plasmids other than the nodulation plasmid are necessary for formation of nitrogen-fixing nodules by Rhizobium leguminosarum. 216 88

Interleukin-1 (IL-1) production by periodic acid (H5IO6)-oxidized human peripheral blood mononuclear (PBMN) cells was assessed by the thymocyte co-mitogenesis assay. Maximum IL-1 levels (approximately 1.2 U/ml) in the conditioned media of PBMN cells were registered within the first 24 hrs post-oxidation, whereas no IL-1 was detected in the media from 24 hrs control cultures. Thymocyte proliferation, driven by periodic acid-induced IL-1, was abolished by an antibody to IL-1 alpha and IL-1 beta. Quantitative analysis of IL-1-containing medium by radioimmunoassay (RIA) indicated that IL-1 beta comprised about 80% of total IL-1. Partial characterization of H5IO6-induced IL-1 beta indicated that it was identical to IL-1 produced by lipopolysaccharide-stimulated macrophages. It is concluded that oxidation of human PBMN cells by H5IO6 triggers synthesis and release of IL-1, most of which was in its IL-1 beta form.
Mol Cell Biochem 1990 Jun 25
PMID:Production of interleukin-1 beta by periodic acid-oxidized human peripheral blood mononuclear cells. 216 43

Endogenous mouse mammary tumor virus (MMTV) proviral transcripts are up regulated during the normal course of B-lymphocyte differentiation. We report here that the regulatory mechanisms which lead to increased levels of MMTV transcripts in differentiating, lipopolysaccharide (LPS)-stimulated normal B cells and in the inducible B-cell lymphoma line CH12 are at least partially distinct from those controlling increases in immunoglobulin and J-chain gene expression. In studies designed to characterize the stimulatory pathways leading to MMTV expression in CH12 cells, we found that stimulation with either LPS or dexamethasone (Dex), a transcriptional activator of MMTV genes, induced not only MMTV expression but also differentiation to antibody secretion. Only Dex-induced and not LPS-induced MMTV expression and differentiation were inhibited by the glucocorticoid antagonist RU486, demonstrating that Dex and LPS stimulate B cells by distinct molecular pathways. Therefore, in B cells, MMTV expression can be regulated via either the conventional hormone receptor-dependent pathway or a hormone receptor-independent pathway. Furthermore, these results suggest that steroid stimulation of B cells can lead to alterations in the expression of other results suggest that steroid stimulation of B cells can lead to alterations in the expression of other steroid-responsive genes that can become involved in the process of B-cell differentiation.
Mol Cell Biol 1990 Aug
PMID:Lipopolysaccharide and dexamethasone induce mouse mammary tumor proviral gene expression and differentiation in B lymphocytes through distinct regulatory pathways. 216 35

A nonvirulent strain of Shigella sonnei phase I has been obtained by integration of the transposon Tn5 into the invasiveness plasmid pSS120 in the virulent strain and designated NR18. The presence of the plasmid pSS120 in both strains results in the similar morphology and bacterial ability to agglutinate in the presence of antiserum to Shigella sonnei phase I antigen. The lipopolysaccharide preparations from the virulent and nonvirulent strains give the similar reactions with the antiserum in the reaction of hemagglutination. However, in the reaction of passive local hemolysis in the gel (Jerne reaction) the significant difference is revealed in the immunogenicity of the preparations, with the preparations from the virulent strain being 4-5 fold more immunogenic. In crossreaction, the antibodies secreted by the mouse spleen cells immunized by LPS from the virulent strain show a weak reaction with the ram erythrocytes sensitized by the LPS of the nonvirulent strain. Thus, the biological changes in the LPS of the nonvirulent strains that are, evidently, the consequence of the structural changes, are identified only by the most sensitive immunological techniques.
Mol Gen Mikrobiol Virusol 1990 Aug
PMID:[Changes in antigenic properties of lipopolysaccharides of Shigella sonnei phase I having lost the virulence due to transposon integration into the invasiveness plasmid PSS120]. 217 9

This study characterizes the interaction of murine macrophage nuclear proteins with the tumor necrosis factor alpha (TNF-alpha) promoter. Gel retardation and methylation interference assays showed that stimulation of TNF-alpha gene transcription in peritoneal exudate macrophages was accompanied by induction of DNA-binding proteins that recognized with different affinities four elements related to the kappa B consensus motif and a Y-box motif. We suggest that the basal level of TNF-alpha expression in macrophages is due to the binding of a constitutive form of NF-kappa B, present at low levels in nuclei from resting thioglycolate exudate peritoneal macrophages, to some if not all of the kappa B motifs; we postulate that this constitutive form contains only the 50-kilodalton (kDa) DNA-binding protein subunits of NF-kappa B, not the 65-kDa protein subunits (P. Baeuerle and D. Baltimore, Genes Dev. 3:1689-1698, 1989). Agents such as glucocorticoids, which decrease TNF-alpha transcription, diminished the basal level of nuclear NF-kappa B. Stimulation of Stimulation of TNF-alpha transcription in macrophages by lipopolysaccharide, gamma interferon, or cycloheximide led to an increased content of nuclear NF-kappa B. This induced factor represents a different form of NF-kappa B, since it generated protein-DNA complexes of slower mobility; we propose that this induced form of NF-kappa B contains both the 50- and 65-kDa protein subunits, the latter ones being necessary to bind NF-kappa B to its cytoplasmic inhibitor in uninduced cells (Baeuerle and Baltimore, Genes Dev., 1989). In resting cells, this inducible form of NF-kappa B was indeed detectable in the cytosol after deoxycholate treatment. UV cross-linking experiments and gel retardation assays indicated that the inducible form of NF-kappa B is in a higher-order complex with other proteins.
Mol Cell Biol 1990 Apr
PMID:Regulation of tumor necrosis factor alpha transcription in macrophages: involvement of four kappa B-like motifs and of constitutive and inducible forms of NF-kappa B. 218 Dec 76

The alveolar macrophage (AMO) in its pivotal position for pulmonary host defense may play a prominent role in the orchestration of polymorphonuclear leukocyte (PMN) diapedesis. We demonstrate that the human AMO may participate in these inflammatory events through the production of a novel neutrophil chemotactic factor, interleukin-8 (IL-8). The induction of AMO-derived IL-8 by tumor necrosis factor (TNF), lipopolysaccharide (LPS), and interleukin-1 (IL-1 beta) was shown to be both dose and time dependent. Maximal IL-8 gene expression, as assessed by Northern blot analyses, was achieved with 20 ng/ml and 1 microgram/ml, respectively, for each of the cytokines and LPS. A kinetic study of TNF-, IL-1 beta-, and LPS-treated AMOs showed significant steady-state IL-8 mRNA accumulation post-stimulation at 1 h, peaking by 8 h, with a decline over the next 16 h. Immunohistochemical staining using rabbit anti-human IL-8 antibody demonstrated significant immunolocalization of cell-associated IL-8 antigen at 4 h, with persistence over the next 20 h. Chemotactic bioactivity peaked by 8 h, with continued production over the next 16 h. Chemotactic bioactivity from AMO-conditioned media was inhibited by IL-8 antiserum by 2, 31, 44, and 47%, respectively, for unstimulated control, LPS-, IL-1 beta-, and TNF-treated cells. Preimmune serum had no effect on chemotactic activity. These data support the central role of the AMO in the elicitation of PMNs into the lung via the production of IL-8.
Am J Respir Cell Mol Biol 1990 Apr
PMID:Human alveolar macrophage gene expression of interleukin-8 by tumor necrosis factor-alpha, lipopolysaccharide, and interleukin-1 beta. 218 81

We characterized the basis for the follicular lymphoproliferation in transgenic mice bearing a Bcl-2-immunoglobulin (Bcl-2-Ig) minigene representing the t(14;18) of human follicular lymphoma. Discriminatory S1 nuclease protection assays revealed that the Bcl-2-Ig transgene was overexpressed relative to endogenous mouse Bcl-2 in spleen and thymus. Western (immunoblot) analysis demonstrated the overproduction of the human 25-kilodalton Bcl-2 protein, which arose from the transgene, in spleen, thymus, and the expanded B-cell subset. Despite the generalized lymphoid pattern of deregulation, two-color flow cytometry and density gradient centrifugation indicated that the expanded lymphocytes were predominantly small, resting B cells coexpressing B220, immunoglobulin M (IgM), IgD, Ia, and kappa. Cell cycle analysis confirmed that about 97% of these expanded B cells reside in G0/G1. An extensive characterization of transgenic lines revealed a fourfold excess of IgM-IgD-expressing B cells in spleen and dramatically increased numbers in bone marrow. While resting, these cells proliferated in response to lipopolysaccharide and anti-IgM and demonstrated normal B-cell colony formation in soft agar. Moreover, these B cells, which demonstrated an extended survival in vitro even in the absence of stroma, were also resting in G0, yet were capable of proliferative responses. These findings provide consistent evidence that the accumulation of B cells after Bcl-2 overproduction is secondary to prolonged cell survival and not increased cell cycling. This suggests a unique role for Bcl-2 as a proto-oncogene that enhances cell survival independent of promoting cell division.
Mol Cell Biol 1990 May
PMID:Deregulated Bcl-2-immunoglobulin transgene expands a resting but responsive immunoglobulin M and D-expressing B-cell population. 218 11

The promoter region of the interleukin-6 (IL-6) gene has a putative NF-kappa B-binding site. We found that a fragment of the IL-6 promoter containing the site specifically binds highly purified NF-kappa B protein and the NF-kappa B protein in nuclear extracts of phorbol ester-induced Jurkat cells. Mutations of the NF-kappa B site abolished complex formation with both purified NF-kappa B and the nuclear extract protein. Transient expression of chloramphenicol acetyltransferase (CAT) plasmids containing the IL-6 promoter revealed very little activity of the promoter in U-937 monocytic cells and in HeLa cells before stimulation. However, stimulation of U-937 and HeLa cells by inducers of NF-kappa B led to a dramatic increase in CAT activity. Mutations in the NF-kappa B-binding site abolished inducibility of IL-6 promoter-cat constructs in U-937 cells by lipopolysaccharide, tumor necrosis factor alpha, the double-stranded RNA poly(IC), or phytohemagglutinin and in HeLa cells by tumor necrosis factor alpha and drastically reduced but did not completely eliminate inducibility in HeLa cells stimulated by double-stranded RNA poly(IC) or phorbol 12-myristate 13-acetate. These results suggest that NF-kappa B is an important mediator for activation of the IL-6 gene by a variety of IL-6 inducers in both U-937 and HeLa cells and that alternative inducible enhancer elements contribute in a cell-specific manner to IL-6 gene induction. Because NF-kappa B is involved in the control of a variety of genes activated upon inflammation, NF-kappa B may play a central role in the inflammatory response to infection and tissue injury.
Mol Cell Biol 1990 May
PMID:Activation of interleukin-6 gene expression through the NF-kappa B transcription factor. 218 31

Neutrophil attractant/activation protein-1 (NAP-1 [interleukin-8]) is an 8,400 D protein that is a chemoattractant and granule release stimulus for neutrophils. NAP-1 was first purified from culture fluids of lipopolysaccharide-stimulated human blood mononuclear leukocytes. It was subsequently isolated from lipopolysaccharide-stimulated lung macrophages, mitogen-stimulated lymphocytes, and virus-infected fibroblasts. Interleukin-1 or tumor necrosis factor induces NAP-1 mRNA in many cells, including monocytes, fibroblasts, and endothelial cells. NAP-1 belongs in a family of host defense small proteins, which have a degree of sequence and structural similarity. Noteworthy are the four half-cystine residues in each protein, which are in register when the protein sequences are suitably aligned. Based on cloning data and N-terminal sequence analyses, NAP-1 is secreted as a 79 residue protein after cleavage of a 20 residue signal peptide. The commonly isolated 77 and 72 residue forms are probably extracellular cleavage products. NAP-1 has considerable charge heterogeneity. Charge and length variants all have chemotactic activity. In contrast to many chemoattractants, NAP-1 does not attract monocytes. Intradermal injection of NAP-1 causes neutrophil infiltration. The wide spectrum of cell sources and production stimuli suggests that NAP-1 mediates neutrophil recruitment in host defense and disease.
Am J Respir Cell Mol Biol 1990 Jun
PMID:Neutrophil attractant/activation protein-1 (NAP-1 [interleukin-8]). 218 53


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