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Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Escherichia coli (E. coli) causes greater than 90% of urinary tract infections, UTI, in childhood. The capacity to adhere to urinary tract epithelial cells characterizes E. coli strains that cause acute pyelonephritis. Adherence of uropathogenic E. coli is the result of a specific interaction between bacterial adhesins and glycolipid receptors on the host cells, especially the globoseries of glycolipids which share the Galactose alpha 1-greater than 4Galactose beta disaccharide (Gal alpha 1-greater than 4Gal beta). In childhood UTI, Gal alpha 1-greater than 4Gal beta-binding bacteria caused significantly higher body temperature, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and pyuria, and lower renal concentrating capacity, than E. coli lacking this specificity. The Gal alpha 1-greater than 4Gal beta-binding bacteria thus appeared to be more potent inducers of inflammation than other strains. Since inflammation may lead to tissue damage we examined the relationship of infection with Gal alpha 1-greater than 4Gal beta-positive bacteria to renal scarring. The frequency of renal scarring was 5% in boys with Gal alpha 1-greater than 4Gal beta-positive and 40% in boys with Gal alpha 1-greater than 4Gal beta-negative E. coli. Bacterial binding to Gal alpha 1-greater than 4Gal beta can be detected with a commercially available test reagent. This reagent can thus be used as an effective predictor of risk for renal scarring. Interleukin-6 (IL-6) is a pyrogen and inducer of the acute phase reactants. It was shown to be produced locally in the urinary tract, in response to UTI, and to spread systemically. Mucosal challenge with dead bacteria was sufficient to induce the IL-6 response. Circulating IL-6, and/or IL-1 and tumor necrosis factor could explain the fever, as well as increased ESR and CRP found in association with acute symptomatic UTI.
APMIS 1990 Dec
PMID:Bacterial adherence as a virulence factor in urinary tract infection. 228 1

Interleukin-6 (IL-6) is a multifunctional cytokine that plays a role in regulation of hematopoiesis. Because IL-6 is coinduced with colony-stimulating factors (CSFs) by various cell types in response to stimulation with IL-1, we investigated whether IL-6 is involved in the IL-1-induced production of CSF by human bone marrow (BM) cells in long-term culture or human fibroblasts. We showed that IL-6 does not induce CSF production by these cells. Neither addition of exogenous IL-6 nor neutralization of endogenous production of IL-6 by an anti-IL-6 monoclonal antibody (MoAb) diminished the IL-1-induced colony-stimulating activity (CSA), indicating that IL-6 did not act synergistically with IL-1. Finally, IL-6 did not influence the kinetics of IL-1-induced CSA production by human fibroblasts. We conclude that IL-6, either alone or in combination with IL-1, does not induce CSF production by human BM stromal cells or fibroblasts.
Blood 1989 Dec
PMID:Interleukin-6 is not involved in the interleukin-1-induced production of colony-stimulating factors by human bone marrow stromal cells and fibroblasts. 247 24

alpha 2-Macroglobulin (alpha 2M) is a broad spectrum protease inhibitor associated with inflammatory responses and proposed to be important in tissue remodeling. alpha 2 M also functions as a carrier of specific growth factors and cytokines, including platelet-derived growth factor, transforming growth factor-beta, basic fibroblast growth factor, interleukin-1, interleukin-6. To determine whether alpha 2M is associated with remodeling phenomena in the rat ovary, the expression of alpha 2M mRNA and protein has been analyzed in specific ovarian cell types during ovulation, luteinization, and luteolysis. Before ovulation, alpha 2M mRNA is not detectable in granulosa cells. Twelve hours after injection of an ovulatory dose of hCG a 5.2-kilobase alpha 2M mRNA is detectable in luteinizing follicles, which is increased further by 48 h and maintained in corpora lutea (CL) for up to 96 h. Administration of PRL from 24-96 h results in both inhibition of luteolysis and marked increases in alpha 2M mRNA in CL, but not in residual tissues, of these same ovaries, isolated 48, 72, and 96 h after an ovulatory dose of hCG, alpha 2M mRNA is also induced by PRL in cultures of luteinized granulosa cells. These changes in alpha 2M mRNA in follicles or developing CL do not appear to reflect the amount of alpha 2M protein present: alpha 2M protein (188K monomer) is present (immunoblot and immunofluorescence data) in small antral and preovulatory follicles even though mRNA is not detectable; after an ovulatory dose of hCG the protein level transiently increases by 12 h (approximately 5-fold) and declines thereafter through 96 h; the decrease in alpha 2M protein observed at 48-96 h is delayed but not abolished by treatment with PRL, even though the mRNA levels continue to rise during this same time period. In contrast, changes in alpha 2M mRNA and protein are regulated coordinately in CL of pregnant rats. alpha 2M mRNA is present, but in low concentration, from days 4-11 of gestation, increases markedly between days 11-21, and decreases at parturition, when functional luteolysis occurs. Hysterectomy of day 10 pregnant rats combined with hormone replacement determined that alpha 2M mRNA levels are regulated primarily by PRL through day 12 and by placental lactogens during midgestation (days 12-15). The increase in alpha 2M mRNA during pregnancy precedes the 40-fold increase (peak) in a alpha 2M protein observed on day 15, which remains elevated through day 21.(ABSTRACT TRUNCATED AT 400 WORDS)
Endocrinology 1989 Dec
PMID:Hormonal regulation and tissue-specific localization of alpha 2-macroglobulin in rat ovarian follicles and corpora lutea. 247 32

Three monoclonal antibodies against human interleukin-6 were established and characterized. One antibody was shown to strongly neutralize both the Ig-inducing and hybridoma/plasmacytoma growth activity of interleukin-6. The results of its epitope analysis using protease treated interleukin-6 and immobilized antibody indicated that this neutralizing antibody binds to a peptide corresponding to Leu151-Lys171 of interleukin-6 molecule. Further analysis using synthetic peptides showed that a shorter peptide corresponding to Ala153-Thr162 can also inhibit the binding of the antibody to interleukin-6. These results suggest that this carboxyl-terminal region plays a crucial role in interleukin-6 functions.
Biochem Biophys Res Commun 1989 Dec 15
PMID:Establishment of strongly neutralizing monoclonal antibody to human interleukin-6 and its epitope analysis. 248 Jul 83

Acute phase reaction is a fast unspecific and highly complex reaction of the animal organism to injury and infection. Main symptoms and metabolic changes are fever, leucocytosis, dramatic rearrangement of plasma protein synthesis in the liver and of the protein synthesis in several other organs. The identification of the liver as main source of plasma proteins lead to the assumption, that the host reaction to the injury, and not the injury itself, is responsible for those changes. Now today, it has been demonstrated, that at least three monokines, mainly produced by cells of the monocyte-macrophage lineage, namely interleukin-1, tumor necrosis factor-alpha and interleukin-6 can mediate the acute phase response. As they can act locally as well as at distant sites in nanomolar concentrations the monokines are considered to be new hormones. Whether other newly recognized macrophage products are also involved in acute phase response has to be clarified.
Z Gastroenterol 1989 Dec
PMID:[Acute phase reaction and its mediators. 1: Interleukin-1]. 248 87

In rat hepatocyte primary cultures recombinant human interleukin-6 (rhIL-6) induced alpha 2-macroglobulin (alpha 2M) synthesis 54-fold. Half-maximal induction was achieved at a rhIL-6 concentration of 30 pM. RhIL-1 beta led only to a 2-fold increase in alpha 2M synthesis, but strongly impaired the action of IL-6. Intraperitoneal injection of rhIL-6 into male rats resulted in a 19.7-fold increase of alpha 2M mRNA already after 4h. In contrast, alpha 2M mRNA levels (50-fold increase) were reached between 16 and 24 h after intramuscular injection of turpentine. Whereas turpentine-induced inflammation resulted in an increased alpha 2M synthesis in male and female rats, rhIL-6 injection had no effect in female rats. The increases after rhIL-6 administration in mRNA concentrations were followed by corresponding changes in alpha 2M levels in serum. By Northern analysis it was demonstrated that LPS-stimulated human monocytes synthesize IL-6 mRNA. The 5'-end of the rat alpha 2M gene has been isolated and the first 3 exons and 166 base pairs of the 5'-flanking region were identified by a combination of oligonucleotide hybridization and DNA sequencing. The transcriptional start site was determined by RNase protection as well as by primer extension experiments. 5'-CATAAAG-3' and 5'-TCAAAA-3' were found as TATA- and CAAT-box equivalent sequences, respectively. Furthermore, a potential glucocorticoid binding site (5'-TGTTCT-3') was localized on the antisense strand of the alpha 2M gene.
Tokai J Exp Clin Med 1988 Dec
PMID:Regulation of alpha 2-macroglobulin gene expression by interleukin-6 (BSF-2/HSF). 248 66

The synthesis of all the major acute phase plasma proteins is stimulated in rat hepatoma and primary cultures of hepatocytes by three, structurally and functionally distinct groups of hormones: 1) hepatocyte-stimulating factors (HSF) and interleukin-6 (IL-6); 2) interleukin-1 (IL-1) and tumor necrosis factor (TNF); and 3) glucocorticoids. Each plasma protein gene requires a specific combination of these 3 hormone types for maximal expression. One set of acute phase proteins, including alpha 2-macroglobulin, alpha 1-antichymotrypsin ( = contrapsin), cysteine protease inhibitor ( = thiostatin), alpha 1-antitrypsin, ceruloplasmin and fibrinogens are predominantly regulated by the keratinocyte-derived HSF-III/-II or IL-6, while a second set of proteins, including alpha 1-acid glycoprotein (AGP), haptoglobin and complement C3 are predominantly regulated by keratinocyte-derived HSF-I, IL-1 or TNF. In conjunction with the above peptide hormones, glucocorticoids synergistically enhance the stimulated expression of most, but not all, acute phase proteins. An exceptionally strong synergy between HSF (or IL-6), IL-1 and glucocorticoids is noted for the activation of the AGP gene. To elucidate the molecular mechanisms of regulation, we have identified the cis-acting genetic elements through which all these hormones control the transcriptional activity of the AGP gene. It appears that acute phase activates a specific nuclear binding protein in the rat liver that interacts with the peptide hormone responsive element located 5 kb upstream of the transcriptional start site.
Tokai J Exp Clin Med 1988 Dec
PMID:Regulation of acute phase protein genes by hepatocyte-stimulating factors, monokines and glucocorticoids. 248 67

Interleukin-6 (IL-6) is involved in the final differentiation of B cells into antibody-producing cells. Recent studies reveal that IL-6 plays an important role in inflammation. Histopathological studies showed that a large number of plasma cells in periodontitis is usually seen in the apical parts of cellular infiltrates beneath the periodontal connective tissues. This evidence suggests that IL-6 may play a critical role in the development of periodontitis. Therefore, we examined IL-6 production in the gingival tissues. Twelve periodontitis patients and five gingivitis patients were included in this study. Nine individuals with healthy periodontium acted as control subjects. Biopsy specimens were dissected into fragments 3 mm in diameter and plated onto 24-well culture plates with RPMI 1640 medium. IL-6 activity in the culture supernatants was measured by IgM production assay using the cell line SKW6-CL4. IL-6 activity was detected at significantly higher levels (P less than 0.001) in culture supernatants from the gingival tissues in periodontitis (23.2 +/- 14.4 units/ml) and gingivititis (12.5 +/- 3.4 units/ml) than in control tissues (2.3 +/- 1.2 units/ml). Subsequently, the relationship between IL-6 activity and clinical stages was examined. The IL-6 levels before initial preparation (23.2 +/- 14.4 units/ml) were significantly higher (P less than 0.001) than those after initial preparation (1.4 +/- 1.8 units/ml), but were not associated with either periodontal pocket depth or the extent of alveolar bone resorption in periodontitis.(ABSTRACT TRUNCATED AT 250 WORDS)
Nihon Shishubyo Gakkai Kaishi 1989 Dec
PMID:[Cytokine production in inflamed human gingival tissues--interleukin-6]. 248 46

Interleukin-6 (IL-6) is a major systemic alarm signal that indicates the occurrence of tissue damage. The IL-6 gene is induced in various cell types by serum, inflammation-associated cytokines, viruses, and second-messenger agonists. There is an overall functional similarity between IL-6 and c-fos promoters, since transfection of excess amounts of either promoter DNA into intact HeLa cells modulates the function of the heterologous promoter construct. Furthermore, the transcription regulatory factor Fos transrepresses both the IL-6 and c-fos promoters. The 115-base pair (bp) region from -225 to -111 in the IL-6 5'-flanking region, which shares nucleotide sequence similarity with the c-fos serum response (SRE) and adjacent AP-1-like (the CGTCA motif) elements, confers responsiveness to several reagents, including serum, forskolin, and phorbol ester, upon the heterologous herpesvirus thymidine kinase (TK) promoter. In gel shift assays using nuclear extracts from HeLa cells, the 115-bp IL-6 enhancer formed several complexes that (i) were increased when extracts from induced HeLa cells were used and (ii) were inhibited most efficiently by the fos E DNA fragment (-700 to -100) and by c-fos oligonucleotides containing an intact AP-1-like site (the CGTCA motif). The 23-bp oligonucleotide designated AR1 from within the IL-6 enhancer region (-173 to -151) contains a CGTCA motif and bound nuclear proteins that also associated with c-fos oligonucleotides containing either an intact SRE or AP-1-like site. A single copy of AR1 inserted upstream of the herpesvirus TK promoter rendered this heterologous promoter inducible by IL-1 alpha, tumor necrosis factor, and serum as well as by activators of the protein kinase A (forskolin) and protein kinase C (phorbol ester) signal transduction pathways. Mutations in the AP-1-like site within AR1 (CGTCA----GTTCA) decreased inducibility of the chimeric IL-6/TK/chloramphenicol acetyltransferase gene by phorbol ester and by forskolin but not by serum, IL-1 alpha, or tumor necrosis factor. These data not only show that the AR1 segment from within the IL-6 enhancer binds nuclear proteins that also bind to c-fos regulatory elements but also demonstrate that a single copy of this 23-bp element is functionally sufficient to confer responsiveness to a variety of inducers and thus define a multiple-response element.
Mol Cell Biol 1989 Dec
PMID:A multiple cytokine- and second messenger-responsive element in the enhancer of the human interleukin-6 gene: similarities with c-fos gene regulation. 251 37

Two cDNA clones encoding a receptor for human granulocyte-macrophage colony-stimulating factor (hGM-CSF-R) were isolated by expression screening of a library made from human placental mRNA. Pools of recombinant plasmid DNA were electroporated into COS cells which were then screened for their capacity to bind radioiodinated hGM-CSF using a sensitive microscopic autoradiographic approach. The cloned GM-CSF-R precursor is a 400 amino acid polypeptide (Mr 45,000) with a single transmembrane domain, a glycosylated extracellular domain and a short (54 amino acids) intracytoplasmic tail. It does not contain a tyrosine kinase domain nor show homology with members of the immunoglobulin super gene family, but does show some significant sequence homologies with receptors for several other haemopoietic growth factors, including those for interleukin-6, erythropoietin and interleukin-2 (beta-chain) and also to the prolactin receptor. When transfected into COS cells the cloned cDNA directed the expression of a GM-CSF-R showing a single class of affinity (KD = 2(-8) nM) and specificity for human GM-CSF but not interleukin-3. Messenger RNA coding for this receptor was detected in a variety of haemopoietic cells known to display hGM-CSF binding, and cross-linking experiments revealed a similar size for the glycosylated receptors in transfected COS and haemopoietic cells.
EMBO J 1989 Dec 01
PMID:Expression cloning of a receptor for human granulocyte-macrophage colony-stimulating factor. 255 71


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