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  • 1.
    Gunaltay, Sezin
    et al.
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Ghiboub, M.
    Frenche Comte Univ, Besancon, France.
    Hultgren, Olof
    Örebro universitet, Institutionen för läkarutbildning.
    Hultgren-Hörnquist, Elisabeth
    Örebro universitet, Institutionen för läkarutbildning.
    The role of IL-37 on cytokine responses downstream of TLR4 and TLR5 signalling in intestinal epithelial cells2014Ingår i: Immunology, ISSN 0019-2805, E-ISSN 1365-2567, Vol. 143, s. 94-95Artikel i tidskrift (Övrigt vetenskapligt)
  • 2.
    Gunaltay, Sezin
    et al.
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Kumawat, Ashok Kumar
    Örebro universitet, Institutionen för hälsovetenskap och medicin. Institute of Infection, College of Medical, Veterinary & Life Sciences, University of Glasgow, Glasgow, United Kingdom.
    Nyhlin, Nils
    Örebro universitet, Institutionen för hälsovetenskap och medicin. Region Örebro län.
    Bohr, Johan
    Örebro universitet, Institutionen för hälsovetenskap och medicin. Region Örebro län.
    Tysk, Curt
    Region Örebro län. Division of Gastroenterology, Department of Medicine, Örebro University, Örebro, Sweden.
    Hultgren, Olof
    Region Örebro län.
    Hultgren-Hörnquist, Elisabeth
    Örebro universitet, Institutionen för läkarutbildning.
    Enhanced levels of chemokines and their receptors in the colon of microscopic colitis patients indicate mixed immune cell recruitment2015Ingår i: Mediators of Inflammation, ISSN 0962-9351, E-ISSN 1466-1861, artikel-id 132458Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Microscopic colitis (MC), comprising collagenous colitis (CC) and lymphocytic colitis (LC), is a common cause of chronic diarrhea. Various immune cell infiltrations in the epithelium and lamina propria are seen in MC immunopathology. We compared gene and protein expressions of different immune cell attracting chemokines and their receptors in colon biopsies from MC patients in active disease or histopathological remission (CC/LC-HR) with controls, using qRT-PCR and Luminex, respectively. CC and LC patients with active disease demonstrated a mixed chemokine profile with significantly enhanced gene and/or protein expressions of the chemokines CCL2, CCL3, CCL4, CCL5, CCL7, CCL22, CXCL8, CXCL9, CXCL10, CXCL11, and CX(3)CL1 and the receptors CCR2, CCR3, CCR4, CXCR1, CXCR2, and CX(3)CR1. Enhanced chemokine/chemokine receptor gene and protein levels in LC-HR patients were similar to LC patients, whereas CC-HR patients demonstrated almost normalized levels. These findings expand the current understanding of the involvement of various immune cells in MC immunopathology and endorse chemokines as potential diagnostic markers as well as therapeutic candidates. Moreover, this study further supports the hypothesis that CC and LC are two different entities due to differences in their immunoregulatory responses.

  • 3.
    Gunaltay, Sezin
    et al.
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Nyhlin, Nils
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Kumawat, Ashok
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Bohr, Johan
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Tysk, Curt
    Örebro University Hospital, Örebro, Sweden.
    Hultgren, Olof
    Örebro universitet, Institutionen för läkarutbildning.
    Hultgren-Hörnquist, Elisabeth
    Örebro universitet, Institutionen för läkarutbildning.
    Increased expression of T cell recruiting chemokines in the colonic mucosa of microscopic colitis patients2013Ingår i: Immunology, ISSN 0019-2805, E-ISSN 1365-2567, Vol. 140, s. 135-135Artikel i tidskrift (Övrigt vetenskapligt)
  • 4.
    Gunaltay, Sezin
    et al.
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Nyhlin, Nils
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Kumawat, Ashok
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Tysk, Curt
    Örebro University Hospital, Örebro, Sweden.
    Bohr, Johan
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Hultgren, Olof
    Örebro universitet, Institutionen för läkarutbildning.
    Hultgren-Hörnquist, Elisabeth
    Örebro universitet, Institutionen för läkarutbildning.
    IL-1/TLR signaling inhibitors in microscopic and ulcerative colitis: Immunopathogenic markers of active disease and remission2013Ingår i: Immunology, ISSN 0019-2805, E-ISSN 1365-2567, Vol. 140, s. 167-167Artikel i tidskrift (Övrigt vetenskapligt)
  • 5.
    Gunaltay, Sezin
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Rademacher, Lech
    Division of Gastroenterology, Department of Medicine, Örebro University Hospital, Örebro, Sweden; Department of Medicine, Avesta Hospital, Avesta, Sweden.
    Hultgren Hörnquist, Elisabeth
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Bohr, Johan
    Örebro universitet, Institutionen för hälsovetenskaper. Region Örebro län. Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Clinical and immunologic effects of faecal microbiota transplantation in a patient with collagenous colitis2017Ingår i: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 23, nr 7, s. 1319-1324Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    One to six percent of patients with microscopic colitis are refractory to medical treatment. The effect of faecal microbiota transplantation (FMT) in active collagenous colitis (CC) has, to the best of our knowledge, never been reported before. Here, we report the effect of repeated FMT in a patient with CC. The patient presented with severe symptoms including profuse diarrhea and profound weight loss. Although she responded to budesonide in the beginning, she became gradually refractory to medical treatment, and was therefore treated with FMT. The patient remained in remission for 11 mo after the third faecal transplantation. The immunomodulatory effect of the therapy was evaluated using flow cytometry, which showed alterations in the profile of intraepithelial and lamina propria lymphocyte subsets after the second transplantation. Our observations indicate that FMT can have an effect in CC, which support the hypothesis that luminal factors, influencing the intestinal microbiota, are involved in the pathogenesis of CC.

  • 6.
    Gunaltay, Sezin
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper. Nutrition-Gut-Brain Interactions Research Centre, Örebro University, Örebro, Sweden.
    Repsilber, Dirk
    Örebro universitet, Institutionen för medicinska vetenskaper. Nutrition-Gut-Brain Interactions Research Centre, Örebro University, Örebro, Sweden.
    Helenius, Gisela
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. Department of Pathology, Örebro University Hospital, Örebro, Sweden.
    Nyhlin, Nils
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. Department of Medicine, Div. of Gastroenterol., Örebro University Hospital, Örebro, Sweden.
    Bohr, Johan
    Department of Medicine, Div of Gastroenterol, Örebro Univ Hosp, Örebro, Sweden; Fac of Med and Hlth, Örebro Univ, Örebro, Sweden.
    Hultgren, Olof
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Microbiology and Immunology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Hultgren Hörnquist, Elisabeth
    Örebro universitet, Institutionen för medicinska vetenskaper. Nutrition-Gut-Brain Interactions Research Centre, Örebro University, Örebro, Sweden.
    Oligoclonal T-cell Receptor Repertoire in Colonic Biopsies of Patients with Microscopic Colitis and Ulcerative Colitis2017Ingår i: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 23, nr 6, s. 932-945Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Microscopic colitis (MC), comprising collagenous colitis (CC) and lymphocytic colitis (LC), is a type of variation of inflammatory bowel diseases. Local T-cell infiltration in the mucosa plays a major role in MC immunopathology.

    Methods: To understand diversity and clonality of infiltrating T cells, we analyzed the T-cell receptor beta (TCR beta) chains in colonic biopsies of MC, ulcerative colitis (UC), and their remission counterparts (CC/LC-HR [histological remission] or UC-R [remission]) compared with patients with non-inflamed colons using next-generation sequencing.

    Results: Compared with controls and patients with CC, patients with LC had significantly lower diversity with significantly lower evenness and richness in TCRVb-Jb gene segments. Similarly, patients with LC-HR had lower diversity because of significantly lower TCRVb-Jb clone richness. Patients with UC and UC-R showed significantly higher diversity and richness. Univariate and multivariate analyses were performed to identify TCRVb-Jb gene segments differentiating disease types from controls or their remission counterparts. Patients with LC were discriminated from controls by 12 clones and from patients with CC by 8 clones. Neither univariate nor multivariate analyses showed significance for patients with CC or CC-HR compared with controls. Patients with UC and UC-R had 16 and 14 discriminating clones, respectively, compared with controls.

    Conclusions: Altogether, patients with MC and UC showed an oligoclonal TCRb distribution. TCRVb-Jb clone types and their diversity were distinctive between patients with CC and LC, as well as for patients with UC, suggesting different pathophysiological mechanisms according to disease type and stage. This study suggests that CC and LC are different entities because of differences in immunoregulatory responses, as mirrored by their T-cell repertoire.

  • 7.
    Günaltay, Sezin
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Dysregulated mucosal immune responses in microscopic colitis patients2016Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Microscopic colitis (MC), comprising collagenous colitis (CC) and lymphocytic colitis (LC) is a common cause of chronic watery diarrhea. The diagnosis relies on typical histopathological changes observed upon microscopic examination. The studies in this thesis investigated innate and adaptive immune responses in the colonic mucosa of MC patients, also comparing patients with active disease (CC and LC) and histopathologically in remission (CC/LC-HR). We first analyzed expression of interleukin-1/Toll-like receptor (IL-1/TLR) signaling regulators in MC patients (Paper I). Our results showed enhanced IRAK-M, microRNA-146a, -155 and -21 expressions, whereas IL-37 gene expression was reduced in CC and LC patients as compared to non-inflamed controls. These results suggest different pathophysiological mechanisms in MC patients. The mixed inflammatory cell infiltrations seen in the lamina propria of MC patients might be a result of dysregulated expression of chemotactic mediators. In Paper II, we showed that MC patients display mainly an increased expression of chemokines and chemokine receptors in active disease as compared to noninflamed controls. In Paper III, we examined if the decreased IL-37 expression seen in Paper I could mediate the upregulation of chemokines seen in Paper II. We showed that a relatively small reduction in the ability of epithelial cells to produce IL-37 results in mainly increased chemokine expressions in a pattern similar to the findings in Paper II. In order to understand the nature of infiltrating T cells commonly observed in MC patients, we analyzed the T cell receptor (TCR) β chains in colonic biopsies of MC patients (Paper IV). Our results showed significant differences in TCRβ repertoire, which suggests selectively expanded T cell clones in active MC and histopathologically in remission patients. Altogether, these results i) increase the knowledge of MC pathogenesis by showing changes in TLR signaling regulators, enhanced chemokine and their receptor expressions involved in a mixed immune cell infiltrations and selectively expanded T cell clones in CC and LC patients, as well as in histopathological remission ii) might potentially increase the possibility of more target-specific therapies based on IL-37 induction, chemokines or chemokine receptor inhibitions, or hindering T cell infiltration according to TCR clonality.

    Delarbeten
    1. Differential expression of interleukin-1/Toll-like receptor signaling regulators in microscopic and ulcerative colitis
    Öppna denna publikation i ny flik eller fönster >>Differential expression of interleukin-1/Toll-like receptor signaling regulators in microscopic and ulcerative colitis
    Visa övriga...
    2014 (Engelska)Ingår i: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 20, nr 34, s. 12249-12259Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    AIM: To investigate Toll-like receptor (TLR) signaling regulators in microscopic and ulcerative colitis patients.

    METHODS: Total RNA and microRNA were isolated from fresh frozen colonic biopsies of non-inflamed controls and patients with active or in-remission collagenous colitis (CC), lymphocytic colitis (LC), or ulcerative colitis (UC). We compared expressions of interleukin-1 receptor-associated kinase (IRAK)-2, IRAK-M, interleukin (IL)-37, microRNA (miR)-146a, miR-155, and miR-21 using quantitative real time reverse transcription polymerase chain reaction.

    RESULTS: IRAK-M expression was increased in LC patients with active disease in histopathological remission (LC-HR; P = 0.02) and UC patients (P = 0.01), but no differences in IRAK-2 expression were detected compared to controls. miR-146a, -155 and -21 expressions were increased in LC-HR (P = 0.04, 0.07, and 0.004) and UC (P = 0.02, 0.04 and 0.03) patients. miR-146a and miR-21 expressions were significantly enhanced in UC patients compared to UC remission (UC-R; P = 0.01 and 0.04). Likewise, active CC patients showed significantly increased expression of miR-155 (P = 0.003) and miR-21 (P = 0.006). IL-37 expression was decreased in both CC (P = 0.03) and LC (P = 0.04) patients with a similar trend in UC patients but not statistically significant, whilst it was increased in UC-R patients compared to controls (P = 0.02) and active UC (P = 0.001).

    CONCLUSION: The identification of differentially expressed miRNAs, IL-37, and IRAK-M suggests different pathophysiologic mechanisms in various disease stages in LC, CC, and UC. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.

    Ort, förlag, år, upplaga, sidor
    WJG Press, 2014
    Nyckelord
    Interleukin-37, MicroRNA, Lymphocytic colitis, Collagenous colitis, Ulcerative colitis
    Nationell ämneskategori
    Gastroenterologi
    Identifikatorer
    urn:nbn:se:oru:diva-37676 (URN)10.3748/wjg.v20.i34.12249 (DOI)000341719100033 ()2-s2.0-84909606787 (Scopus ID)
    Anmärkning

    Funding Agencies:

    Research Committee of Örebro County Council

    Örebro University

    Tillgänglig från: 2014-10-13 Skapad: 2014-10-13 Senast uppdaterad: 2019-03-26Bibliografiskt granskad
    2. Enhanced levels of chemokines and their receptors in the colon of microscopic colitis patients indicate mixed immune cell recruitment
    Öppna denna publikation i ny flik eller fönster >>Enhanced levels of chemokines and their receptors in the colon of microscopic colitis patients indicate mixed immune cell recruitment
    Visa övriga...
    2015 (Engelska)Ingår i: Mediators of Inflammation, ISSN 0962-9351, E-ISSN 1466-1861, artikel-id 132458Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Microscopic colitis (MC), comprising collagenous colitis (CC) and lymphocytic colitis (LC), is a common cause of chronic diarrhea. Various immune cell infiltrations in the epithelium and lamina propria are seen in MC immunopathology. We compared gene and protein expressions of different immune cell attracting chemokines and their receptors in colon biopsies from MC patients in active disease or histopathological remission (CC/LC-HR) with controls, using qRT-PCR and Luminex, respectively. CC and LC patients with active disease demonstrated a mixed chemokine profile with significantly enhanced gene and/or protein expressions of the chemokines CCL2, CCL3, CCL4, CCL5, CCL7, CCL22, CXCL8, CXCL9, CXCL10, CXCL11, and CX(3)CL1 and the receptors CCR2, CCR3, CCR4, CXCR1, CXCR2, and CX(3)CR1. Enhanced chemokine/chemokine receptor gene and protein levels in LC-HR patients were similar to LC patients, whereas CC-HR patients demonstrated almost normalized levels. These findings expand the current understanding of the involvement of various immune cells in MC immunopathology and endorse chemokines as potential diagnostic markers as well as therapeutic candidates. Moreover, this study further supports the hypothesis that CC and LC are two different entities due to differences in their immunoregulatory responses.

    Nationell ämneskategori
    Cell- och molekylärbiologi Immunologi inom det medicinska området
    Forskningsämne
    Immunologi
    Identifikatorer
    urn:nbn:se:oru:diva-44605 (URN)10.1155/2015/132458 (DOI)000353128700001 ()2-s2.0-84928473938 (Scopus ID)
    Anmärkning

    Funding Agencies:

    Örebro University Hospital Research Foundation (Nyckelfonden)

    Research Committee, Orebro County Council

    Örebro University

    Tillgänglig från: 2015-05-12 Skapad: 2015-05-12 Senast uppdaterad: 2018-06-30Bibliografiskt granskad
    3. Reduced Il-37 production increases the spontaneous chemokine expressions in colon epithelial cells
    Öppna denna publikation i ny flik eller fönster >>Reduced Il-37 production increases the spontaneous chemokine expressions in colon epithelial cells
    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Nationell ämneskategori
    Annan medicinsk grundvetenskap
    Forskningsämne
    Biomedicin
    Identifikatorer
    urn:nbn:se:oru:diva-47897 (URN)
    Tillgänglig från: 2016-02-02 Skapad: 2016-02-02 Senast uppdaterad: 2018-01-10Bibliografiskt granskad
    4. Oligoclonal T cell receptor repertoire in colonic biopsies of microscopic and ulcerative colitis patients
    Öppna denna publikation i ny flik eller fönster >>Oligoclonal T cell receptor repertoire in colonic biopsies of microscopic and ulcerative colitis patients
    Visa övriga...
    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Nationell ämneskategori
    Annan medicinsk grundvetenskap
    Forskningsämne
    Biomedicin
    Identifikatorer
    urn:nbn:se:oru:diva-47898 (URN)
    Tillgänglig från: 2016-02-02 Skapad: 2016-02-02 Senast uppdaterad: 2018-01-10Bibliografiskt granskad
  • 8.
    Günaltay, Sezin
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Ghiboub, Mohammed
    School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; Academic Medical Center, Tytgat Institute for Liver and Intestinal Research, Amsterdam University, Amsterdam, The Netherlands..
    Hultgren, Olof
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. Department of Microbiology and Immunology, Örebro University Hospital, Örebro, Sweden.
    Hultgren Hörnquist, Elisabeth
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Reduced IL-37 Production Increases Spontaneous Chemokine Expressions in Colon Epithelial Cells2017Ingår i: Digestive Diseases and Sciences, ISSN 0163-2116, E-ISSN 1573-2568, Vol. 62, nr 5, s. 1204-1215Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background and Aim: Microscopic colitis, comprising collagenous colitis and lymphocytic colitis, is a common cause of chronic diarrhea. Previously, we showed enhanced chemokine productions in microscopic colitis patients, indicating dysregulated immune cell chemotaxis in the immunopathogenesis. We also showed decreased mRNA of IL-37, mainly regarded as an anti-inflammatory cytokine, in the colonic mucosa of these patients, potentially an important factor for the chronicity of the colitis. Our aim in this study was to understand the possible role of IL-37 in chemokine production using a cell line model.

    Methods: A colon epithelial cell line, T84, was stimulated with the TLR5 ligand flagellin. IL-37 protein production was reduced 20% using the CRISPR/Cas9 system, and the changes in chemokine mRNA and protein expressions were compared to cells transfected with empty plasmid.

    Results: The 20% reduction in IL-37 protein levels spontaneously increased CCL5, CXCL8, CXCL10, and CXCL11 mRNA and protein expressions. CCL2 mRNA and protein levels were enhanced upon TLR5 stimulation. CCL3, CCL20, and CX3CL1 mRNA expressions were increased either spontaneously or following TLR5 stimulation, whereas CCL4 and CCL22 mRNA expressions were significantly decreased.

    Conclusions: Even a minor decrease in the ability of colon epithelial cells to produce IL-37 results in altered chemokine expression, mainly an increase in the production of several chemokines. Our results indicate that a decreased IL-37 expression by colon epithelial cells may be an important factor for increasing the recruitment of immune cells and subsequently developing microscopic colitis.

  • 9.
    Günaltay, Sezin
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Ghiboub, Mohammed
    Amsterdam university.
    Hultgren, Olof
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Hultgren-Hörnquist, Elisabeth
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Reduced Il-37 production increases the spontaneous chemokine expressions in colon epithelial cellsManuskript (preprint) (Övrigt vetenskapligt)
  • 10.
    Günaltay, Sezin
    et al.
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Nyhlin, Nils
    Örebro universitet, Institutionen för hälsovetenskap och medicin. Region Örebro län. Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Kumawat, Ashok Kumar
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Tysk, Curt
    Region Örebro län. Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Bohr, Johan
    Örebro universitet, Institutionen för hälsovetenskap och medicin. Region Örebro län. Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Hultgren, Olof
    Örebro universitet, Institutionen för läkarutbildning. Region Örebro län. Department of Microbiology and Immunology, Örebro University Hospital, Örebro, Sweden.
    Hultgren-Hörnquist, Elisabeth
    Örebro universitet, Institutionen för läkarutbildning.
    Differential expression of interleukin-1/Toll-like receptor signaling regulators in microscopic and ulcerative colitis2014Ingår i: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 20, nr 34, s. 12249-12259Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    AIM: To investigate Toll-like receptor (TLR) signaling regulators in microscopic and ulcerative colitis patients.

    METHODS: Total RNA and microRNA were isolated from fresh frozen colonic biopsies of non-inflamed controls and patients with active or in-remission collagenous colitis (CC), lymphocytic colitis (LC), or ulcerative colitis (UC). We compared expressions of interleukin-1 receptor-associated kinase (IRAK)-2, IRAK-M, interleukin (IL)-37, microRNA (miR)-146a, miR-155, and miR-21 using quantitative real time reverse transcription polymerase chain reaction.

    RESULTS: IRAK-M expression was increased in LC patients with active disease in histopathological remission (LC-HR; P = 0.02) and UC patients (P = 0.01), but no differences in IRAK-2 expression were detected compared to controls. miR-146a, -155 and -21 expressions were increased in LC-HR (P = 0.04, 0.07, and 0.004) and UC (P = 0.02, 0.04 and 0.03) patients. miR-146a and miR-21 expressions were significantly enhanced in UC patients compared to UC remission (UC-R; P = 0.01 and 0.04). Likewise, active CC patients showed significantly increased expression of miR-155 (P = 0.003) and miR-21 (P = 0.006). IL-37 expression was decreased in both CC (P = 0.03) and LC (P = 0.04) patients with a similar trend in UC patients but not statistically significant, whilst it was increased in UC-R patients compared to controls (P = 0.02) and active UC (P = 0.001).

    CONCLUSION: The identification of differentially expressed miRNAs, IL-37, and IRAK-M suggests different pathophysiologic mechanisms in various disease stages in LC, CC, and UC. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.

  • 11.
    Günaltay, Sezin
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Repsilber, Dirk
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Helenius, Gisela
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Nyhlin, Nils
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Bohr, Johan
    Örebro universitet, Institutionen för hälsovetenskaper.
    Hultgren-Hörnquist, Elisabeth
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Oligoclonal T cell receptor repertoire in colonic biopsies of microscopic and ulcerative colitis patientsManuskript (preprint) (Övrigt vetenskapligt)
  • 12.
    Jayaprakash, Kartheyaene
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Demirel, Isak
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Gunaltay, Sezin
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Khalaf, Hazem
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Bengtsson, Torbjörn
    Örebro universitet, Institutionen för medicinska vetenskaper.
    PKC, ERK/p38 MAP kinases and NF-B targeted signalling play a role in the expression and release of IL-1β  and CXCL8 in Porphyromonas gingivalis-infected THP1 cells2017Ingår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 125, nr 7, s. 623-633Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Porphyromonas gingivalis is a keystone pathogen in periodontitis and is gaining importance in cardiovascular pathogenesis. Protease-activated receptors (PARs), toll-like receptors (TLRs) and nucleotide-binding oligomerization domain (NOD) on monocytes recognize the structural components on P. gingivalis, inducing inflammatory intermediates. Here, we elucidate the modulation of PARs, TLRs, NODs, and the role of MAPK and NF-B in IL-1 and CXCL8 release. THP1 cells were stimulated with P. gingivalis wild-type W50 and its isogenic gingipain mutants: Rgp mutant E8 and Kgp mutant K1A. We observed modulation of PARs, TLRs, NOD, IL-1 and CXCL8 expression by P. gingivalis. Gingipains hydrolyse IL-1 and CXCL8, which is more evident for IL-1 accumulation at 24 h. Inhibition of PKC (protein kinase C), p38 and ERK (extracellular signal-regulated kinases) partially reduced P. gingivalis-induced IL-1 at 6 h, whereas PKC and ERK reduced CXCL8 at both 6 and 24 h. Following NF-B inhibition, P. gingivalis-induced IL-1 and CXCL8 were completely suppressed to basal levels. Overall, TLRs, PARs and NOD possibly act in synergy with PKC, MAPK ERK/p38 and NF-B in P. gingivalis-induced IL-1 and CXCL8 release from THP1 cells. These pro-inflammatory cytokines could affect leucocytes in circulation and exacerbate other vascular inflammatory conditions such as atherosclerosis.

  • 13.
    Jayaprakash, Kartheyaene
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Demirel, Isak
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Gunaltay, Sezin
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Khalaf, Hazem
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Bengtsson, Torbjörn
    Örebro universitet, Institutionen för medicinska vetenskaper.
    PKC, ERK/p38 MAP kinases and NF-κB targeted signalling plays a crucial role in expression and release of IL-1β and CXCL8 in Porphyromonas gingivalis infected monocytesManuskript (preprint) (Övrigt vetenskapligt)
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