Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Stx family contains two types called Stx1 (verotoxin 1: VT1 or Shiga-like toxin: SLT1) and Stx2 (VT2, SLT2); both toxins are encoded by bacteriophages. Stx1 is identical to Shiga toxin produced by Shigella dysenteriae type I. Stx2 is heterogeneous and immunologically different from Stx1. Although many variations are found in Stx family, all Stx has an A-B structure: the A subunit has N-glycosidase activity and the B subunit binds to a membrane glycolipid, globotriaosylceramide (Gb3). The A subunit cleaves a single adenine residue from the 28S rRNA component of eukaryotic ribosomes, resulting in inhibition of protein synthesis. Stx-producing Escherichia coli (STEC) is known to cause hemorrhagic enterocolitis and hemolytic-uremic syndrome (HUS). Stx plays a role in the occurrence of blood in the feces and in the HUS by their action on the endothelial cells of blood vessels in the intestinal submucosa and in the renal glomeruli. Epidemiologically, Stx2 seems to be more important than Stx1 in development of HUS. The action of Stx is not limited to inhibition of protein synthesis. Stx induces macrophages to express tumor necrosis factor alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and interleukin-6 (IL-6) in vitro. These cytokines and lipopolysaccharide (LPS) are reported to increase the susceptibility of cells to Stx. A variety of cells such as tubular epithelial cells, may be targets for Stx-mediated apoptosis. Apoptosis is considered to contribute to the pathogenesis of HUS caused by STEC. In this review, recent progress in Stx-related research is summarized.
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PMID:Escherichia coli Shiga toxin. 1099 31

Porin of Shigella dysenteriae type 1 increased the mRNA levels for Toll-like receptor (TLR) 2 and TLR6 by 1.5- and 2.9-fold respectively, of peritoneal cavity B-1a and B-1b cells, implicating that coexpression of TLR2 and TLR6 is essential as a combinatorial repertoire for recognition of porin by the B-1 cells. Among the two key TLRs, TLR2 and TLR4, which are primarily responsible for recognizing majority of the bacterial products, TLR2 and not TLR4, participates in porin recognition. TLR2 got increased on both the B-1 cell populations whereas the TLR4 expression remained unaffected. Besides TLRs, mRNA for MyD88, an effector molecule associated with TLR-mediated response was enhanced by 1.8-fold that suggests of its involvement in the activity of porin. Both of the B-1 cell populations expressed strongly the mRNA for NF-kappaB in the presence of porin, that was 2.4-fold more than untreated control, conforming to the earlier finding that coexpression of TLR2 and TLR6, resulted in robust NF-kappaB activation for signaling. Porin treatment of B-1 cell populations of C57BL/6 mice, and C3H/HeJ mice in particular, selectively up-regulated the expression of the costimulatory molecules. CD80 expression got enhanced on the B-1a cells whereas CD86 got solely expressed on B-1b cells. Porin-induced cell surface expression of IgM and IgA on B-1 cell populations from C57BL/6 mice. The IgA-generating capacity, hallmark of mucosal immune response, was confirmed with B-1 cells of C3H/HeJ, the lipopolysaccharide non-responder mouse, in response to the protein. The porin-mediated induction of IgA was augmented by interleukin-6 on B-1a and B-1b cells, by 2.4- and 2.6-fold, respectively. The IgA expressed on both B-1a and B-1b cell surfaces after 72 h of culture was found to bind to the 38 kDa monomer of porin confirming it to be anti-porin IgA antibody.
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PMID:Up-regulation of CD80-CD86 and IgA on mouse peritoneal B-1 cells by porin of Shigella dysenteriae is Toll-like receptors 2 and 6 dependent. 1548 52

Porin of Shigella dysenteriae type 1 increased the mRNA levels for Toll-like receptors TLR2 and TLR6, by 1.8-fold and twofold, respectively, in peritoneal cavity B-2 cells from C57BL/6 mice, implicating that the co-expression of TLR2 and TLR6 occurs as a combinatorial repertoire in response to porin. Among the two key TLRs, TLR2 and TLR4, which are primarily responsible for recognizing the majority of bacterial products, TLR2 alone participates in porin recognition. TLR2 expression was increased on B-2 cells, whereas the expression of TLR4 remained unaffected. Besides TLRs, mRNA for myeloid differentiation factor 88 (MyD88), an effector molecule associated with the TLR-mediated response, was enhanced by twofold, suggesting its involvement in the activity of porin. The B-2 cells showed a 1.8-fold increase in mRNA expression of the signalling molecule, nuclear factor-kappa B (NF-kappaB), in the presence of porin. Porin treatment of B-2 cells selectively up-regulated the expression of the costimulatory molecule, CD86, by 4.4-fold. Porin induced the cell-surface expression of immunoglobulin (Ig)M, of IgG2a preferentially among the IgG subclasses, and of IgA, on B-2 cells. The porin-mediated inductions of IgG2a and IgA were augmented by interleukin-6 on B-2 cells, by 2.7- and 1.6-fold, respectively.
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PMID:Porin of Shigella dysenteriae enhances Toll-like receptors 2 and 6 of mouse peritoneal B-2 cells and induces the expression of immunoglobulin M, immunoglobulin G2a and immunoglobulin A. 1560 99

Shigella dysenteriae causes the most severe of all infectious diarrhoeas and colitis. We infected rhesus macaques orally and also treated them orally with a small and non-absorbable polypropyletherimine dendrimer glucosamine that is a Toll-like receptor-4 (TLR4) antagonist. Antibiotics were not given for this life-threatening infection. Six days later, the clinical score for diarrhoea, mucus and blood was 54% lower, colon interleukin-8 and interleukin-6 were both 77% lower, and colon neutrophil infiltration was 75% less. Strikingly, vasculitis did not occur and tissue fibrin thrombi were reduced by 67%. There was no clinical toxicity or adverse effect of dendrimer glucosamine on systemic immunity. This is the first report in non-human primates of the therapeutic efficacy of a small and orally bioavailable TLR antagonist in severe infection. Our results show that an oral TLR4 antagonist can enable controlled resolution of the infection-related-inflammatory response and can also prevent neutrophil-mediated gut wall necrosis in severe infectious diarrhoeas.
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PMID:Controlling the cytokine storm in severe bacterial diarrhoea with an oral Toll-like receptor 4 antagonist. 2649 44