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Publikasjoner (3 av 3) Visa alla publikasjoner
Pietz, G., De, R., Hedberg, M., Sjöberg, V., Sandström, O., Hernell, O., . . . Hammarström, M.-L. (2017). Immunopathology of childhood celiac disease: Key role of intestinal epithelial cells. PLoS ONE, 12(9), Article ID e0185025.
Åpne denne publikasjonen i ny fane eller vindu >>Immunopathology of childhood celiac disease: Key role of intestinal epithelial cells
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2017 (engelsk)Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, nr 9, artikkel-id e0185025Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

BACKGROUND & AIMS: Celiac disease is a chronic inflammatory disease of the small intestine mucosa due to permanent intolerance to dietary gluten. The aim was to elucidate the role of small intestinal epithelial cells in the immunopathology of celiac disease in particular the influence of celiac disease-associated bacteria.

METHODS: Duodenal biopsies were collected from children with active celiac disease, treated celiac disease, and clinical controls. Intestinal epithelial cells were purified and analyzed for gene expression changes at the mRNA and protein levels. Two in vitro models for human intestinal epithelium, small intestinal enteroids and polarized tight monolayers, were utilized to assess how interferon-γ, interleukin-17A, celiac disease-associated bacteria and gluten influence intestinal epithelial cells.

RESULTS: More than 25 defense-related genes, including IRF1, SPINK4, ITLN1, OAS2, CIITA, HLA-DMB, HLA-DOB, PSMB9, TAP1, BTN3A1, and CX3CL1, were significantly upregulated in intestinal epithelial cells at active celiac disease. Of these genes, 70% were upregulated by interferon-γ via the IRF1 pathway. Most interestingly, IRF1 was also upregulated by celiac disease-associated bacteria. The NLRP6/8 inflammasome yielding CASP1 and biologically active interleukin-18, which induces interferon-γ in intraepithelial lymphocytes, was expressed in intestinal epithelial cells.

CONCLUSION: A key factor in the epithelial reaction in celiac disease appears to be over-expression of IRF1 that could be inherent and/or due to presence of undesirable microbes that act directly on IRF1. Dual activation of IRF1 and IRF1-regulated genes, both directly and via the interleukin-18 dependent inflammasome would drastically enhance the inflammatory response and lead to the pathological situation seen in active celiac disease.

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Identifikatorer
urn:nbn:se:umu:diva-139860 (URN)10.1371/journal.pone.0185025 (DOI)000411339900076 ()28934294 (PubMedID)
Tilgjengelig fra: 2017-09-25 Laget: 2017-09-25 Sist oppdatert: 2018-06-09bibliografisk kontrollert
Bitar, A., De, R., Melgar, S., Aung, K. M., Rahman, A., Qadri, F., . . . Hammarström, M.-L. (2017). Induction of immunomodulatory miR-146a and miR-155 in small intestinal epithelium of Vibrio cholerae infected patients at acute stage of cholera. PLoS ONE, 12(3), Article ID 0173817.
Åpne denne publikasjonen i ny fane eller vindu >>Induction of immunomodulatory miR-146a and miR-155 in small intestinal epithelium of Vibrio cholerae infected patients at acute stage of cholera
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2017 (engelsk)Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, nr 3, artikkel-id 0173817Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

The potential immunomodulatory role of microRNAs in small intestine of patients with acute watery diarrhea caused by Vibrio cholerae O1 or enterotoxigenic Escherichia coli (ETEC) infection was investigated. Duodenal biopsies were obtained from study-participants at the acute (day 2) and convalescent (day 21) stages of disease, and from healthy individuals. Levels of miR-146a, miR-155 and miR-375 and target gene (IRAK1, TRAF6, CARD10) and 11 cytokine mRNAs were determined by qRT-PCR. The cellular source of microRNAs in biopsies was analyzed by in situ hybridization. The ability of V. cholerae bacteria and their secreted products to cause changes in microRNA- and mRNA levels in polarized tight monolayers of intestinal epithelial cells was investigated. miR-146a and miR-155 were expressed at significantly elevated levels at acute stage of V. cholerae infection and declined to normal at convalescent stage (P<0.009 versus controls; P = 0.03 versus convalescent stage, pairwise). Both microRNAs were mainly expressed in the epithelium. Only marginal down-regulation of target genes IRAK1 and CARD10 was seen and a weak cytokine-profile was identified in the acute infected mucosa. No elevation of microRNA levels was seen in ETEC infection. Challenge of tight monolayers with the wild type V. cholerae O1 strain C6706 and clinical isolates from two study-participants, caused significant increase in miR-155 and miR-146a by the strain C6706 (P<0.01). One clinical isolate caused reduction in IRAK1 levels (P<0.05) and none of the strains induced inflammatory cytokines. In contrast, secreted factors from these strains caused markedly increased levels of IL-8, IL-1β, and CARD10 (P<0.001), without inducing microRNA expression. Thus, miR-146a and miR-155 are expressed in the duodenal epithelium at the acute stage of cholera. The inducer is probably the V. cholerae bacterium. By inducing microRNAs the bacterium can limit the innate immune response of the host, including inflammation evoked by its own secreted factors, thereby decreasing the risk of being eliminated.

HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-133013 (URN)10.1371/journal.pone.0173817 (DOI)000398945800031 ()28319200 (PubMedID)
Tilgjengelig fra: 2017-03-28 Laget: 2017-03-28 Sist oppdatert: 2018-06-09bibliografisk kontrollert
De, R., Ramamurthy, T., Sarkar, B. L., Mukhopadhyay, A. K., Pazhani, G. P., Sarkar, S., . . . Nair, G. B. (2017). Retrospective genomic analysis of Vibrio cholerae O1 El Tor strains from different places in India reveals the presence of ctxB-7 allele found in Haitian isolates. Epidemiology and Infection, 145(11), 2212-2220
Åpne denne publikasjonen i ny fane eller vindu >>Retrospective genomic analysis of Vibrio cholerae O1 El Tor strains from different places in India reveals the presence of ctxB-7 allele found in Haitian isolates
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2017 (engelsk)Inngår i: Epidemiology and Infection, ISSN 0950-2688, E-ISSN 1469-4409, Vol. 145, nr 11, s. 2212-2220Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

A total of 45 strains of Vibrio cholerae O1 isolated from 10 different places in India where they were associated with cases of cholera between the years 2007 and 2008 were examined by molecular methods. With the help of phenotypic and genotypic tests the strains were confirmed to be O1 El Tor biotype strains with classical ctxB gene. Polymerase chain reaction (PCR) analysis by double - mismatch amplification mutation assay PCR showed 16 of these strains carried the ctxB-7 allele reported in Haitian strains. Sequencing of the ctxB gene in all the 45 strains revealed that in 16 strains the histidine at the 20th amino acid position had been replaced by asparagine and this single nucleotide polymorphism did not affect cholera toxin production as revealed by beads enzyme-linked immunosorbent assay. This study shows that the new ctxB gene sequence was circulating in different places in India. Seven representatives of these 45 strains analysed by pulsed - field gel electrophoresis showed four distinct Not I digested profiles showing that multiple clones were causing cholera in 2007 and 2008.

sted, utgiver, år, opplag, sider
Cambridge University Press, 2017
Emneord
ctxB-7, molecular typing, PFGE, Surveillance, Vibrio cholerae
HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-139820 (URN)10.1017/S0950268817001182 (DOI)000409124100005 ()28712383 (PubMedID)
Tilgjengelig fra: 2017-09-25 Laget: 2017-09-25 Sist oppdatert: 2018-06-09bibliografisk kontrollert
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