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Mo1713 The Role of the Galectin-1 in the Pathogenesis of IBD
AGA Abstracts
to counterbalance the NOD2 increase induced by inflammation. Future work will be done to assess whether NOD2 is a direct target of both miR-320a and -320b and to analyse possible correlations between NOD2 and miR320 expression in inflamed tissues of IBD patients. References 1.Fasseu M, Tréton X, Guichard C, et al. Identification of restricted subsets of mature microRNA abnormally expressed in inactive colonic mucosa of patients with inflammatory bowel disease. PLoS One 2010; 5:1-12. 2.Chen Y, Wang C, Liu Y, et al. miR-122 targets NOD2 to decrease intestinal epithelial cell injury in Crohn's disease. Biochem Biophys Res Commun 2013; 438:133-9.
Mo1714 Designer Thiopurine Analogues for Optimized Immunosuppressive Therapy of Inflammatory Bowel Disease Imke Atreya, Alexandra Diall, Radovan Dvorsky, Mathias Gruen, Ute Hofmann, Elke Schaeffeler, Christian Henninger, Raja Atreya, Ulrike Billmeier, Clemens Neufert, Stefanie Zenker, Rocio Lopez-Posadas, Ilse Daehn, Gerhard Fritz, Matthias Schwab, Markus F. Neurath Introduction: The clinical use of azathioprine and 6-mercaptopurine in IBD therapy is limited by their delayed onset of action and potential side effects such as myelosuppression and hepatotoxicity. As these drugs specifically target the Vav1/ Rac1 signaling pathway in lamina propria T lymphocytes via their metabolite 6-thio-GTP, we studied expression and optimized suppression of this pathway in IBD. Methods: Rac1 and Vav1 expression was analyzed in mucosal immune cells in IBD patients. Targeted molecular modelling of the 6-thio-GTP molecule was performed to optimize Rac1 blockade. 44 modified thiopurine designer analogues were tested for apoptosis induction, potential toxicity and immunosuppression. Results: A significantly increased number of Vav1 positive immune cells as well as higher levels of Vav1 mRNA expression could be detected in inflamed colon tissue of IBD patients indicating upregulation of Vav1 in IBD colitis. As Vav1 activity on Rac1 is the molecular target of 6-mercaptopurine, we next focused on the identification of more potent inhibitors of Vav1/ Rac1 interaction and 6-thio-GTP was chosen as parent compound for subsequent molecular modelling. Indeed, several of the newly designed thiopurine analogues induced significantly higher T cell apoptosis than 6-mercaptopurine. We identified a lead compound, denoted B-0N, based on its superior capacity to mediate earlier and stronger induction of apoptosis in peripheral blood T cells than 6-mercaptopurine. As functional characteristics of T cells located in the gut lamina propria differ markedly from those of peripheral T cells, the described immunosuppressive capacity of B-0N was confirmed in intestinal lamina propria mononuclear cells. Indeed, B-0N induced significantly more apoptotic cell death in lamina propria immune cells from the inflamed gut of IBD patients as compared to 6mercaptopurine. Furthermore, B-0N treatment resulted in accelerated inhibition of Rac1 activity in primary peripheral blood T cells and also mediated higher levels of Rac1 inhibition in intestinal lamina propria immune cells. Compared to 6-thio-GTP and 6-mercaptopurine, B-0N treatment was associated with decreased in vitro myelo- and hepatotoxicity. Performed cell culture experiments furthermore implicated that the favorable toxicity profile of B-0N can potentially be explained by the fact that B-0N exposed cells showed significantly decreased levels of 6-TG incorporation into cellular DNA and subsequently only milder levels of DNA damage compared to 6-thio-GTP treated cells. Conclusion: The Vav1/ Rac1 pathway is activated in mucosal immune cells in IBD. The designer thiopurine analogue B-0N induces immunosuppression more potently than 6-mercaptopurine. Collectively, our findings suggest that thiopurine analogues such as B-0N may represent a novel class of immunosuppressive agents for optimized therapy of IBD.
Mo1712 Kruppel-Like Factor Klf10 Regulates Transforming Growth Factor Receptor Signaling in CD8+ Cytotoxic T Lymphocytes Konstantinos A. Papadakis, James Krempski, Maneesh Dave, Phyllis A. Svingen, William A. Faubion Background: TGF-beta is a pleitrophic cytokine with diverse effects on many cell types and a general regulatory role in the immune system. KLF10 and is a critical regulator in the transcriptional network controlling TGF-β1 and in CD4+CD25- T cells and T regs. The role of KLF10 in regulating CD8+ T cell responses, however, is currently unknown. Methods: We analyzed the phenotype and effector function of KLF10-deficient T cells and analyzed the ability to induce wasting disease upon transfer to RAG1-/- mice. We further explore the underlying pathobiology of the role of KLF10 in regulating TGF-beta receptor expression in T cells. Results: Adult KLF10-deficient animals have an increased frequency of effector or memory T cells, defined by the expression of CD44 and CD62L in both the CD4+ and CD8+ T cell compartment in the spleen. This correlated with higher expression of the T helper type 1 cell-associated transcription factor T-bet. The higher expression of T-bet in KLF10-/- T cells correlated with higher production of IFN-γ following in vitro stimulation compared to wt T cells. KLF10-deficient animals, however, develop normally and they don't show any signs of autoimmunity. Since the phenotype of KLF10-deficient T cells resembled that seen in TGF-βRII-deficient mice, we examined the role of KLF10 in regulating TGFβRII expression and signaling in T cells. We found that freshly isolated CD4+ and CD8+ T cells from the spleen and Small Intestine (SI) of adult mice express lower levels of surface TGF-β-RII expression as analyzed by flow cytometry. In vitro activation of CD8+ T cells up-regulate TGF-β RII to a lesser extent in KLF10-deficient compared to WT CD8+ T cells. Moreover, TGF-β stimulation of KLF10- deficient CD8+ T cells leads to lower Smad-2 phosphorylation compared to WT CD8+ T cells. Collectively, our data suggest that KLF10 plays a critical role in the regulation of TGF-β RII following TCR activation and subsequently TGF-β signaling. We further explored the proliferative responses of KLF10-/- CD8+ T cells to TCR stimulation and cytokines. KLF10-/- CD8+ T cells respond more vigorously to TCR and IL-15 stimulation compared to Wt CD8+ T cells. To determine the proliferate responses in a lymphopenic environment we transferred a mixed population of KLF10-/- and Wt CD8+ T cells in 1:1 ratio into RAG1-/- mice and analyzed their expansion 7 days later. KLF10-/- CD8+ T cells expanded significantly more compared to Wt CD8+ T cells after transfer into RAG1-/- mice. Transfer of KLF10-/- T cells into RAG1-/- mice, however, did not induce wasting disease indicating a residual TGF-beta signaling in these cell in vivo after transfer that prevents the development of autoimmunity. Conclusion: KLF10 is critically involved in the regulation of TGF-beta receptor II (TGRII) in peripheral and mucosal CD8+ T cells.
Mo1715 Role of Receptor Interacting Protein 2 (Rip-2) in IL17 Production and STAT3 Activation in ETBF Induced Colitis Shervin Rabizadeh, Hanlin L. Wang, Kenichi Shimada, Shuang Chen, Timothy Crother, Stephan Targan, Cynthia L. Sears, Moshe Arditi Intro: Enterotoxigenic Bacteroides fragilis (ETBF), a molecular subtype of the human commensal B. fragilis, induces murine colitis with strong infiltration of the lamina propria with IL17-producing CD4+ T cells (Th17) and Stat 3 (signal transducer and activator of transcription 3) activation. Stat3 and Th17 appear to be important players in inflammatory bowel disease (IBD) making ETBF induced colitis an ideal model for understanding the immunology of IBD. The IBD susceptibility protein nucleotide oligomerization domain protein 2 (Nod2) binds to the protein kinase receptor-interacting protein 2 (Rip2) to coordinate cytokine responses. Herein we studied the role of the innate immune protein Rip2 in ETBF induced colitis. Methods: Rip2 deficient and wild type mice were intragastrically inoculated with 108 CFU of ETBF after receiving 1-3 days of antibiotics to enhance colonization. Mice were euthanized 5-7 days post inoculation with the bacterium. Gastrointestinal (GI) tissue and/ or spleen was ‘flash frozen' in liquid nitrogen for subsequent extraction of nuclear proteins and/or RNA extraction for qt-PCR, dissected for extraction of lymphocytes for flow cytometry, or preserved in 10% formalin for routine histopathology (scored for inflammation and proliferation on a scale of 0-27). Immunohistochemistry (IHC; scored 0-4) and Western blot were used to detect phosphorylated (activated) Stat3 (pStat3). Results: Histopathologic colitis induced by ETBF was significantly reduced in Rip2 deficient mice compared to wild type mice in both the cecum (12.8 vs 8.5, p <0.0001) and colon (6.4 vs 3, p<0.03). ETBF colonization was similar (~1010 colony forming units/gm stool) in both groups. Interestingly Il-17a gene expression was higher in the cecum and colon of Rip2 deficient mice compared to wild type and flow cytometric analysis also revealed increased IL-17A production by CD4+ cells in the spleen of Rip2 deficient mice compared to wild type (5.8% vs 3.5%). In contrast, Stat3 activation was reduced in Rip2 deficient mice cecum and colon, particularly in colonic epithelial cells as measured by IHC (0.9 vs 1.7, p<0.002; and 0.7 vs 1.5, p<0.005) and Western analysis. Discussion: Innate immune protein Rip2 appears to contribute to ETBF-induced colitis. ETBF mice without functioning Rip2 had attenuated inflammation. Interestingly, these mice have increased IL-17A production with decreased Stat3 activation. In the absence of Rip2, the colon appears to have a higher production of IL-17A after exposure to a human commensal organism possibly shedding light on the aberrant immunological responses of IBD patients with Nod2 genetic alteration. Future work will define the specific cell types producing IL-17A in the colon of Rip2 deficient mice and whether transcriptional pathways other than Stat3 promote IL-17 production in the setting of Nod2 deficiency.
Mo1713 The Role of the Galectin-1 in the Pathogenesis of IBD Rodrigo Papa Gobbi, Alicia M. Sambuelli, Andres Rocca, Cecilia Muglia, Renata Curciarello, Gabriel A. Rabinovich, Marta A. Toscano, Anibal H. Gil, Silvia M. Negreira, Sergio P. Huernos, Silvina A. Goncalves, Maricel I. Bellicoso, Tirado Pablo, Martin Yantorno, Andres Irigoyen, Guillermo H. Docena BACKGROUND: Inflammatory bowel diseases (IBD) are multifactorial disorders characterized by a chronic and relapsing intestinal inflammation. Galectin-1, a ubiquitous endogenous lectin, has been implicated in several chronic inflammatory disorders. AIM: We aimed to analyze its role in the colonic mucosa of patients with Crohn′s disease (CD) and Ulcerative colitis (UC). MATERIAL AND METHODS: Gal-1 expression was studied by qPCR, immunoblotting and histology in biopsies and resected tissues of patients with IBD (n=26) and control patients (n=20). Gal-1-specific binding ligands were also analyzed by flow cytometry in lamina propria and its physiologycal role in the induction of cell death was evaluated by flow cytometry. RESULTS: We found in 21 biopsies of CD and 22 biopsies of CU that Gal1 mRNA expression was increased in colonic inflamed areas (p<0.01). However Gal-1 protein expression was lower as compared to non-inflamed areas. To clarify this controversial finding we cultured control biopsies with TNF-α (1, 5 and 10 ng/mL) and observed a doseresponse increase in the expression and secretion of Gal-1 (p<0.05). Additionally, fibroblast supernatants from IBD patients show the ability to cleave Gal-1 protein. Both findings could explain the dissociation between mRNA expression and protein secretion. Gal-1-specific binding sites were considerably reduced in isolated lamina propria CD4 or CD8 lymphocytes from inflamed areas (n=11), as compared to non-inflamed areas (n=10) or control samples (n=8) (p<0.05). A consistent lower binding of PNA and C2GnT-1 expression was found in IBD samples, suggesting lower levels of asialo-core 1-O-glycans. When apoptosis was analyzed we found that 10 ng Gal-1 increased the frequency of annexin-1-positive cells in control patients (n=6) (17,94% with medium and 32,94 with 10 ng Gal-1. p<0,05). Nevertheless no increased in the frequency of annexin-1-positive cells was observed in inflamed areas of IBD patients (n=5, p=0,9647). CONCLUSIONS: In conclusion, we found a differential expression of Gal-1 and Gal-1-specific glycosylated ligands in biological samples of IBD. We also found that Gal-1 exerts a pro-apoptotic effect in T lymphocytes from non-inflamed areas, whereas T cells from inflamed areas are refractory to cell death. The reduced expression of this protein in inflamed areas and the absence of Gal-1-specific sites may have relevant implications in the survival vs cell death of mucosal T lymphocytes. This might impact in the persistency of the inflammatory process in the affected colon.
AGA Abstracts
S-642
to counterbalance the NOD2 increase induced by inflammation. Future work will be done to assess whether NOD2 is a direct target of both miR-320a and -320b and to analyse possible correlations between NOD2 and miR320 expression in inflamed tissues of IBD patients. References 1.Fasseu M, Tréton X, Guichard C, et al. Identification of restricted subsets of mature microRNA abnormally expressed in inactive colonic mucosa of patients with inflammatory bowel disease. PLoS One 2010; 5:1-12. 2.Chen Y, Wang C, Liu Y, et al. miR-122 targets NOD2 to decrease intestinal epithelial cell injury in Crohn's disease. Biochem Biophys Res Commun 2013; 438:133-9.
Mo1714 Designer Thiopurine Analogues for Optimized Immunosuppressive Therapy of Inflammatory Bowel Disease Imke Atreya, Alexandra Diall, Radovan Dvorsky, Mathias Gruen, Ute Hofmann, Elke Schaeffeler, Christian Henninger, Raja Atreya, Ulrike Billmeier, Clemens Neufert, Stefanie Zenker, Rocio Lopez-Posadas, Ilse Daehn, Gerhard Fritz, Matthias Schwab, Markus F. Neurath Introduction: The clinical use of azathioprine and 6-mercaptopurine in IBD therapy is limited by their delayed onset of action and potential side effects such as myelosuppression and hepatotoxicity. As these drugs specifically target the Vav1/ Rac1 signaling pathway in lamina propria T lymphocytes via their metabolite 6-thio-GTP, we studied expression and optimized suppression of this pathway in IBD. Methods: Rac1 and Vav1 expression was analyzed in mucosal immune cells in IBD patients. Targeted molecular modelling of the 6-thio-GTP molecule was performed to optimize Rac1 blockade. 44 modified thiopurine designer analogues were tested for apoptosis induction, potential toxicity and immunosuppression. Results: A significantly increased number of Vav1 positive immune cells as well as higher levels of Vav1 mRNA expression could be detected in inflamed colon tissue of IBD patients indicating upregulation of Vav1 in IBD colitis. As Vav1 activity on Rac1 is the molecular target of 6-mercaptopurine, we next focused on the identification of more potent inhibitors of Vav1/ Rac1 interaction and 6-thio-GTP was chosen as parent compound for subsequent molecular modelling. Indeed, several of the newly designed thiopurine analogues induced significantly higher T cell apoptosis than 6-mercaptopurine. We identified a lead compound, denoted B-0N, based on its superior capacity to mediate earlier and stronger induction of apoptosis in peripheral blood T cells than 6-mercaptopurine. As functional characteristics of T cells located in the gut lamina propria differ markedly from those of peripheral T cells, the described immunosuppressive capacity of B-0N was confirmed in intestinal lamina propria mononuclear cells. Indeed, B-0N induced significantly more apoptotic cell death in lamina propria immune cells from the inflamed gut of IBD patients as compared to 6mercaptopurine. Furthermore, B-0N treatment resulted in accelerated inhibition of Rac1 activity in primary peripheral blood T cells and also mediated higher levels of Rac1 inhibition in intestinal lamina propria immune cells. Compared to 6-thio-GTP and 6-mercaptopurine, B-0N treatment was associated with decreased in vitro myelo- and hepatotoxicity. Performed cell culture experiments furthermore implicated that the favorable toxicity profile of B-0N can potentially be explained by the fact that B-0N exposed cells showed significantly decreased levels of 6-TG incorporation into cellular DNA and subsequently only milder levels of DNA damage compared to 6-thio-GTP treated cells. Conclusion: The Vav1/ Rac1 pathway is activated in mucosal immune cells in IBD. The designer thiopurine analogue B-0N induces immunosuppression more potently than 6-mercaptopurine. Collectively, our findings suggest that thiopurine analogues such as B-0N may represent a novel class of immunosuppressive agents for optimized therapy of IBD.
Mo1712 Kruppel-Like Factor Klf10 Regulates Transforming Growth Factor Receptor Signaling in CD8+ Cytotoxic T Lymphocytes Konstantinos A. Papadakis, James Krempski, Maneesh Dave, Phyllis A. Svingen, William A. Faubion Background: TGF-beta is a pleitrophic cytokine with diverse effects on many cell types and a general regulatory role in the immune system. KLF10 and is a critical regulator in the transcriptional network controlling TGF-β1 and in CD4+CD25- T cells and T regs. The role of KLF10 in regulating CD8+ T cell responses, however, is currently unknown. Methods: We analyzed the phenotype and effector function of KLF10-deficient T cells and analyzed the ability to induce wasting disease upon transfer to RAG1-/- mice. We further explore the underlying pathobiology of the role of KLF10 in regulating TGF-beta receptor expression in T cells. Results: Adult KLF10-deficient animals have an increased frequency of effector or memory T cells, defined by the expression of CD44 and CD62L in both the CD4+ and CD8+ T cell compartment in the spleen. This correlated with higher expression of the T helper type 1 cell-associated transcription factor T-bet. The higher expression of T-bet in KLF10-/- T cells correlated with higher production of IFN-γ following in vitro stimulation compared to wt T cells. KLF10-deficient animals, however, develop normally and they don't show any signs of autoimmunity. Since the phenotype of KLF10-deficient T cells resembled that seen in TGF-βRII-deficient mice, we examined the role of KLF10 in regulating TGFβRII expression and signaling in T cells. We found that freshly isolated CD4+ and CD8+ T cells from the spleen and Small Intestine (SI) of adult mice express lower levels of surface TGF-β-RII expression as analyzed by flow cytometry. In vitro activation of CD8+ T cells up-regulate TGF-β RII to a lesser extent in KLF10-deficient compared to WT CD8+ T cells. Moreover, TGF-β stimulation of KLF10- deficient CD8+ T cells leads to lower Smad-2 phosphorylation compared to WT CD8+ T cells. Collectively, our data suggest that KLF10 plays a critical role in the regulation of TGF-β RII following TCR activation and subsequently TGF-β signaling. We further explored the proliferative responses of KLF10-/- CD8+ T cells to TCR stimulation and cytokines. KLF10-/- CD8+ T cells respond more vigorously to TCR and IL-15 stimulation compared to Wt CD8+ T cells. To determine the proliferate responses in a lymphopenic environment we transferred a mixed population of KLF10-/- and Wt CD8+ T cells in 1:1 ratio into RAG1-/- mice and analyzed their expansion 7 days later. KLF10-/- CD8+ T cells expanded significantly more compared to Wt CD8+ T cells after transfer into RAG1-/- mice. Transfer of KLF10-/- T cells into RAG1-/- mice, however, did not induce wasting disease indicating a residual TGF-beta signaling in these cell in vivo after transfer that prevents the development of autoimmunity. Conclusion: KLF10 is critically involved in the regulation of TGF-beta receptor II (TGRII) in peripheral and mucosal CD8+ T cells.
Mo1715 Role of Receptor Interacting Protein 2 (Rip-2) in IL17 Production and STAT3 Activation in ETBF Induced Colitis Shervin Rabizadeh, Hanlin L. Wang, Kenichi Shimada, Shuang Chen, Timothy Crother, Stephan Targan, Cynthia L. Sears, Moshe Arditi Intro: Enterotoxigenic Bacteroides fragilis (ETBF), a molecular subtype of the human commensal B. fragilis, induces murine colitis with strong infiltration of the lamina propria with IL17-producing CD4+ T cells (Th17) and Stat 3 (signal transducer and activator of transcription 3) activation. Stat3 and Th17 appear to be important players in inflammatory bowel disease (IBD) making ETBF induced colitis an ideal model for understanding the immunology of IBD. The IBD susceptibility protein nucleotide oligomerization domain protein 2 (Nod2) binds to the protein kinase receptor-interacting protein 2 (Rip2) to coordinate cytokine responses. Herein we studied the role of the innate immune protein Rip2 in ETBF induced colitis. Methods: Rip2 deficient and wild type mice were intragastrically inoculated with 108 CFU of ETBF after receiving 1-3 days of antibiotics to enhance colonization. Mice were euthanized 5-7 days post inoculation with the bacterium. Gastrointestinal (GI) tissue and/ or spleen was ‘flash frozen' in liquid nitrogen for subsequent extraction of nuclear proteins and/or RNA extraction for qt-PCR, dissected for extraction of lymphocytes for flow cytometry, or preserved in 10% formalin for routine histopathology (scored for inflammation and proliferation on a scale of 0-27). Immunohistochemistry (IHC; scored 0-4) and Western blot were used to detect phosphorylated (activated) Stat3 (pStat3). Results: Histopathologic colitis induced by ETBF was significantly reduced in Rip2 deficient mice compared to wild type mice in both the cecum (12.8 vs 8.5, p <0.0001) and colon (6.4 vs 3, p<0.03). ETBF colonization was similar (~1010 colony forming units/gm stool) in both groups. Interestingly Il-17a gene expression was higher in the cecum and colon of Rip2 deficient mice compared to wild type and flow cytometric analysis also revealed increased IL-17A production by CD4+ cells in the spleen of Rip2 deficient mice compared to wild type (5.8% vs 3.5%). In contrast, Stat3 activation was reduced in Rip2 deficient mice cecum and colon, particularly in colonic epithelial cells as measured by IHC (0.9 vs 1.7, p<0.002; and 0.7 vs 1.5, p<0.005) and Western analysis. Discussion: Innate immune protein Rip2 appears to contribute to ETBF-induced colitis. ETBF mice without functioning Rip2 had attenuated inflammation. Interestingly, these mice have increased IL-17A production with decreased Stat3 activation. In the absence of Rip2, the colon appears to have a higher production of IL-17A after exposure to a human commensal organism possibly shedding light on the aberrant immunological responses of IBD patients with Nod2 genetic alteration. Future work will define the specific cell types producing IL-17A in the colon of Rip2 deficient mice and whether transcriptional pathways other than Stat3 promote IL-17 production in the setting of Nod2 deficiency.
Mo1713 The Role of the Galectin-1 in the Pathogenesis of IBD Rodrigo Papa Gobbi, Alicia M. Sambuelli, Andres Rocca, Cecilia Muglia, Renata Curciarello, Gabriel A. Rabinovich, Marta A. Toscano, Anibal H. Gil, Silvia M. Negreira, Sergio P. Huernos, Silvina A. Goncalves, Maricel I. Bellicoso, Tirado Pablo, Martin Yantorno, Andres Irigoyen, Guillermo H. Docena BACKGROUND: Inflammatory bowel diseases (IBD) are multifactorial disorders characterized by a chronic and relapsing intestinal inflammation. Galectin-1, a ubiquitous endogenous lectin, has been implicated in several chronic inflammatory disorders. AIM: We aimed to analyze its role in the colonic mucosa of patients with Crohn′s disease (CD) and Ulcerative colitis (UC). MATERIAL AND METHODS: Gal-1 expression was studied by qPCR, immunoblotting and histology in biopsies and resected tissues of patients with IBD (n=26) and control patients (n=20). Gal-1-specific binding ligands were also analyzed by flow cytometry in lamina propria and its physiologycal role in the induction of cell death was evaluated by flow cytometry. RESULTS: We found in 21 biopsies of CD and 22 biopsies of CU that Gal1 mRNA expression was increased in colonic inflamed areas (p<0.01). However Gal-1 protein expression was lower as compared to non-inflamed areas. To clarify this controversial finding we cultured control biopsies with TNF-α (1, 5 and 10 ng/mL) and observed a doseresponse increase in the expression and secretion of Gal-1 (p<0.05). Additionally, fibroblast supernatants from IBD patients show the ability to cleave Gal-1 protein. Both findings could explain the dissociation between mRNA expression and protein secretion. Gal-1-specific binding sites were considerably reduced in isolated lamina propria CD4 or CD8 lymphocytes from inflamed areas (n=11), as compared to non-inflamed areas (n=10) or control samples (n=8) (p<0.05). A consistent lower binding of PNA and C2GnT-1 expression was found in IBD samples, suggesting lower levels of asialo-core 1-O-glycans. When apoptosis was analyzed we found that 10 ng Gal-1 increased the frequency of annexin-1-positive cells in control patients (n=6) (17,94% with medium and 32,94 with 10 ng Gal-1. p<0,05). Nevertheless no increased in the frequency of annexin-1-positive cells was observed in inflamed areas of IBD patients (n=5, p=0,9647). CONCLUSIONS: In conclusion, we found a differential expression of Gal-1 and Gal-1-specific glycosylated ligands in biological samples of IBD. We also found that Gal-1 exerts a pro-apoptotic effect in T lymphocytes from non-inflamed areas, whereas T cells from inflamed areas are refractory to cell death. The reduced expression of this protein in inflamed areas and the absence of Gal-1-specific sites may have relevant implications in the survival vs cell death of mucosal T lymphocytes. This might impact in the persistency of the inflammatory process in the affected colon.
AGA Abstracts
S-642