Olfactomedin-4 is a glycoprotein secreted into mucus in active IBD

Slides:

Advertisements

Similar presentations

High and increasing prevalence of inflammatory bowel disease in Finland with a clear North–South difference Airi Jussila, Lauri J. Virta, Veikko Salomaa,

Advertisements

Volume 130, Issue 2, Pages (February 2006)

Volume 132, Issue 1, Pages (January 2007)

Substance P Mediates Proinflammatory Cytokine Release From Mesenteric Adipocytes in Inflammatory Bowel Disease Patients Aristea Sideri, Kyriaki Bakirtzi,

Validation of a point-of-care desk top device to quantitate fecal calprotectin and distinguish inflammatory bowel disease from irritable bowel syndrome

YouTube® and inflammatory bowel disease

Patients with ulcerative colitis responding to steroid treatment up-regulate glucocorticoid receptor levels in colorectal mucosa L. Flood, E. Innala,

High and increasing prevalence of inflammatory bowel disease in Finland with a clear North–South difference Airi Jussila, Lauri J. Virta, Veikko Salomaa,

Prevalence of irritable bowel syndrome (IBS) in first-degree relatives of patients with inflammatory bowel disease (IBD) Mariam Aguas, Vicente Garrigues,

Validation of a point-of-care desk top device to quantitate fecal calprotectin and distinguish inflammatory bowel disease from irritable bowel syndrome

Association of a Nkx2-3 polymorphism with Crohn's disease and expression of Nkx2-3 is up-regulated in B cell lines and intestinal tissues with Crohn's.

Expression and functional analysis of intestinal organic cation/l-carnitine transporter (OCTN) in Crohn's Disease Marc Girardin, Serge Dionne, Philippe.

Anterior ischemic optic neuropathy in a patient with Crohn's disease and aberrant MTHFR and GPIIIa gene variants T. Felekis, K.H. Katsanos, C.D. Zois,

Serum prohepcidin levels in chronic inflammatory bowel diseases

N. Kjaersgaard Nielsen, V. Wewer, L. Skafte, A. Paerregaard

Filiform polyposis associated with sigmoid diverticulitis in a patient without inflammatory bowel disease Hyun-Soo Kim, Kil Yeon Lee, Youn Wha Kim Journal.

Public awareness of Crohn's disease and ulcerative colitis: A national survey Sieglinde Angelberger, Harald Vogelsang, Gottfried Novacek, Wolfgang Miehsler,

Validation of a point-of-care desk top device to quantitate fecal calprotectin and distinguish inflammatory bowel disease from irritable bowel syndrome

Volume 136, Issue 2, Pages e5 (February 2009)

Activated thrombin activatable fibrinolysis inhibitor (TAFIa) is associated with inflammatory markers in inflammatory bowel diseases Danuta Owczarek,

Volume 133, Issue 6, Pages (December 2007)

Volume 129, Issue 1, Pages (July 2005)

Volume 130, Issue 1, Pages (January 2006)

Volume 135, Issue 5, Pages e24 (November 2008)

Volume 141, Issue 6, Pages (December 2011)

Volume 124, Issue 5, Pages (May 2003)

Patients with ulcerative colitis responding to steroid treatment up-regulate glucocorticoid receptor levels in colorectal mucosa L. Flood, E. Innala,

Hong Wei Chu, MDa, Monica Kraft, MDa, James E. Krause, PhDb, Michael D

Volume 133, Issue 6, Pages (December 2007)

Volume 132, Issue 1, Pages (January 2007)

Paula Borralho, Ana Vieira, João Freitas, Paula Chaves, Jorge Soares

Volume 115, Issue 6, Pages (December 1998)

Osteoporosis in inflammatory bowel disease

Volume 115, Issue 2, Pages (August 1998)

Volume 124, Issue 5, Pages (May 2003)

Pediatric pulmonary Crohn's disease: More frequent than expected

Suppurative granulomatous inflammation in the ileo-anal pouch

Validation of a point-of-care desk top device to quantitate fecal calprotectin and distinguish inflammatory bowel disease from irritable bowel syndrome

A Chromosome 8 Gene-Cluster Polymorphism with Low Human Beta-Defensin 2 Gene Copy Number Predisposes to Crohn Disease of the Colon Klaus Fellermann,

Pathogenic Escherichia coli in inflammatory bowel diseases

Volume 119, Issue 6, Pages (December 2000)

Plasminogen activator inhibitor-1 is increased in colonic epithelial cells from patients with colitis-associated cancer Earl Gillespie, Susan E. Leeman,

Association of a Nkx2-3 polymorphism with Crohn's disease and expression of Nkx2-3 is up-regulated in B cell lines and intestinal tissues with Crohn's.

Yinghong Wang, Hua Gong, Rocio Lopez, Lei Lian, Ravi P. Kiran, Edy E

Complete remission of a primary rectal lymphoma on ulcerative colitis, after withdrawal of azathioprine and infliximab Antonio López San Román, Manuel.

Volume 130, Issue 2, Pages (February 2006)

Health-related quality of life in inflammatory bowel disease: Psychosocial, clinical, socioeconomic, and demographic predictors Anilga Moradkhani, Linda.

A novel NF-κB inhibitor, dehydroxymethylepoxyquinomicin, ameliorates inflammatory colonic injury in mice Tohru Funakoshi, Kenichiro Yamashita, Nobuki.

Volume 139, Issue 3, Pages e3 (September 2010)

Potential role of protease-activated receptor-2-stimulated activation of cytosolic phospholipase A2 in intestinal myofibroblast proliferation: Implications.

Volume 129, Issue 2, Pages (August 2005)

Volume 142, Issue 4, Pages e2 (April 2012)

Volume 81, Issue 3, Pages (February 2012)

Volume 117, Issue 5, Pages (November 1999)

Volume 62, Issue 1, Pages (July 2002)

P. Harding, L. Balasubramanian, J. Swegan, A. Stevens, W.F. Glass

Volume 128, Issue 7, Pages (June 2005)

Differential Gene Induction of Human β-Defensins (hBD-1, -2, -3, and -4) in Keratinocytes Is Inhibited by Retinoic Acid Jürgen Harder, Ulf Meyer-Hoffert,

Volume 132, Issue 2, Pages (February 2007)

Volume 130, Issue 2, Pages (February 2006)

BMP-4 Upregulates Kit Expression in Mouse Melanoblasts prior to the Kit-Dependent Cycle of Melanogenesis Tamihiro Kawakami, Satoko Kimura, Yoko Kawa,

Interferon-γ-Mediated Growth Regulation of Melanoma Cells: Involvement of STAT1- Dependent and STAT1-Independent Signals Anja Bosserhoff Journal of Investigative.

Pimecrolimus Enhances TLR2/6-Induced Expression of Antimicrobial Peptides in Keratinocytes Amanda S. Büchau, Jürgen Schauber, Thomas Hultsch, Anton Stuetz,

Volume 114, Issue 6, Pages (June 1998)

Volume 136, Issue 7, Pages (June 2009)

Intestinal myofibroblasts in innate immune responses of the intestine

Triptolide is a potent suppressant of C3, CD40 and B7h expression in activated human proximal tubular epithelial cells Yuzhi Hong, Wuding Zhou, Ke Li,

Volume 139, Issue 1, Pages (July 2010)

Differences in proliferation of the hematopoietic cell line TF-1 and cytokine production by peripheral blood leukocytes induced by 2 naturally occurring.

A Chromosome 8 Gene-Cluster Polymorphism with Low Human Beta-Defensin 2 Gene Copy Number Predisposes to Crohn Disease of the Colon Klaus Fellermann,

Presentation transcript:

Olfactomedin-4 is a glycoprotein secreted into mucus in active IBD Michael Gersemann, Svetlana Becker, Sabine Nuding, Lena Antoni, German Ott, Peter Fritz, Naohide Oue, Wataru Yasui, Jan Wehkamp, Eduard F. Stange Journal of Crohn's and Colitis Volume 6, Issue 4, Pages 425-434 (May 2012) DOI: 10.1016/j.crohns.2011.09.013 Copyright © 2011 European Crohn's and Colitis Organisation Terms and Conditions

Figure 1 IL-8, OLFM4, Muc1 and Hath1 expression in controls and IBD mucosa: IL-8 transcripts are enhanced in inflamed vs. noninflamed CD and UC without significant differences between both diseases (A). OLFM4 mRNA was significantly more induced in UC than CD (B). Muc1 transcripts are augmented more in inflamed vs. noninflamed CD than in UC (C). Hath1 mRNA is significantly downregulated in inflamed UC (D). OLFM4 is highly correlated with IL-8 (E, r=0.68 for all samples, p<0.001) but not with Hath1 (F, r=−0.17 for all samples, ns; squares = controls, triangles = CD, circles = UC; *: p<0.05 (these significances are lost after Bonferroni correction), **: p<0.01, ***: p<0.001). Journal of Crohn's and Colitis 2012 6, 425-434DOI: (10.1016/j.crohns.2011.09.013) Copyright © 2011 European Crohn's and Colitis Organisation Terms and Conditions

Figure 2 OLFM4 immunostaining in controls and IBD mucosa: OLFM4 staining is located in the lower third of the crypt in control samples (A, magnification 100-fold) and expanded up to the epithelial surface during inflammation (B = inflamed CD, C = inflamed UC, magnification 100-fold). Journal of Crohn's and Colitis 2012 6, 425-434DOI: (10.1016/j.crohns.2011.09.013) Copyright © 2011 European Crohn's and Colitis Organisation Terms and Conditions

Figure 3 OLFM4 Dot Blot analysis in controls and IBD mucosa: OLFM4 protein is significantly increased in inflamed CD and even more pronounced in inflamed UC biopsy samples as compared to controls (top lane: recombinant OLFM4 in increasing amounts from left to right: 0.05, 0.1, 0.5 and 1μg). Journal of Crohn's and Colitis 2012 6, 425-434DOI: (10.1016/j.crohns.2011.09.013) Copyright © 2011 European Crohn's and Colitis Organisation Terms and Conditions

Figure 4 Secreted OLFM4 in controls and IBD mucus: OLFM4 is found in the crypt lumen (A = CD, arrows, magnification 200-fold) and also in the surface mucus (B = UC, arrows, magnification 200-fold). Dot Blot analysis demonstrates OLFM4 in rectal mucus extracts (C, top lane: recombinant OLFM4 in increasing concentrations from left to right: 0.05, 0.1 and 0.5μg). Journal of Crohn's and Colitis 2012 6, 425-434DOI: (10.1016/j.crohns.2011.09.013) Copyright © 2011 European Crohn's and Colitis Organisation Terms and Conditions

Figure 5 OLFM4 binding to HBD1-3: Coincubation of OLFM4 with HBD1-3, but not bovine serum albumin (BSA), resulted in a dose dependent increase of OLFM4 absorption (*: p<0.05, ***: p<0.001). Journal of Crohn's and Colitis 2012 6, 425-434DOI: (10.1016/j.crohns.2011.09.013) Copyright © 2011 European Crohn's and Colitis Organisation Terms and Conditions

Figure 6 OLFM4 expression in LS174T cells incubated with E. coli Nissle (EcN) in the presence and absence of the γ-secretase inhibitor dibenzazepine (DBZ). 24h of incubation with EcN led to a significant increase of OLFM4 transcripts. Treatment with DBZ led to a significant downregulation of OLFM4 transcripts after 24h. DBZ blocked the stimulation by EcN. Values are compared to controls at the given time-point set to 1 (*: p<0.05, **: p<0.01). This experiment was performed for 4 times in triplicates. Journal of Crohn's and Colitis 2012 6, 425-434DOI: (10.1016/j.crohns.2011.09.013) Copyright © 2011 European Crohn's and Colitis Organisation Terms and Conditions