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Sa1749 Investigating the Role of Interferon Regulatory Factor 8 in Helicobacter pylori-Induced Inflammatory Responses
Sa1748
Cationic Amino Acid Transporter 2 and L-Arginine Availability Are Required for Talin-1-Dependent Adherence of the Colonic Pathogen Citrobacter Rodentium and Subsequent Pro-Inflammatory Responses Kshipra Singh, Lori A. Coburn, Jennifer P. Druce, Mohammad Asim, Daniel P. Barry, Rupesh Chaturvedi, Keith T. Wilson
Comparative Behaviour of Macrophages Isolated From Patients With Crohn's Disease or Ulcerative Colitis and Controls in Response to Adherent-Invasive or Non-Pathogenic E. Coli Infection Emilie Vazeille, Anthony Buisson, Marion Goutte, Lemlih Ouchchane, Jean-Pierre Hugot, Amélie de Vallée, Gilles Bommelaer, Arlette Darfeuille-Michaud
Background: L-arginine (L-Arg) uptake in cells is mediated by cationic amino acid transporter (CAT) proteins, and CAT2 is the inducible form. We have found that CAT2-/- mice exhibit less colitis in the IBD model induced by infection with Citrobacter rodentium, a rodent pathogen similar to EPEC that acts by forming attaching and effacing lesions on epithelial cells. The translocated intimin receptor is injected into host cells by C. rodentium and forms a complex with talin-1 that mediates bacterial binding and downstream signaling. Our aim was to investigate the role of talin-1 in C. rodentium infection. Methods: Male C57BL/6 wild-type (WT) or CAT2-/- mice were infected with C. rodentium for 14 days. Talin-1 and the C. rodentium protein espB were assesed by confocal microscopy and Western blotting. mRNA levels of talin-1 and the proinflammatory CXC chemokines, KC and MIP-2, were determined by qPCR. Young adult mouse colon (YAMC) cells were transduced with control or talin-1 shRNA, and activated with C. rodentium at an MOI of 200. Bacterial adherence was assessed by culture after saponin treatment of cells. Levels of the NF-κB subunit p65 were assessed by immunofluorescence at 30 min, and of talin-1, KC and MIP-2 by qPCR at 4 h. Talin-1 mRNA stability was assessed in YAMC cells using the transcriptional inhibitor actinomycin D followed by serial assessment of mRNA levels. Results: C. rodentium infection in vivo induced a 4-fold increase in talin-1 mRNA and protein expression in whole tissues and a 236-fold increase in mRNA levels in colonic epithelial cells (CECs). Talin-1 and espB protein levels were markedly decreased in colon tissues from infected CAT2-/- vs. WT mice; this was confirmed by confocal microscopy and there was also less colocalization of these proteins. Talin-1, KC and MIP-2 mRNA levels were each decreased by >92% in CAT2-/- vs. WT mice (p<0.01). L-lysine, a competitive inhibitor of L-Arg uptake, reduced induction of talin-1, KC, and MIP-2 mRNA expression by 60.4 ± 18.3%, 91.7 ± 2.6%, and 68.9 ± 12.2%, respectively, in YAMC cells (p<0.01). In talin-1 knockdown cells, levels of adherent C. rodentium decreased from 4.9 ± 0.9 to 0.8 ± 0.2 bacteria/cell (p<0.05), and there was less nuclear translocation of p65. Similarly, KC and MIP-2 levels were decreased by 90.6 ± 0.3% and 92.5 ± 3.1%, respectively, in knockdown cells (p<0.01). There was a 4.2 ± 0.5-fold increase in talin-1 mRNA levels when cells starved of L-Arg were repleted with L-Arg for 4 h. Talin-1 mRNA was less stable in the absence of L-Arg; the mRNA half-life was 5.2fold (p<0.01) greater in cells repleted with L-Arg. Conclusions: Talin-1 is essential for C. rodentium adherence to colonic epithelial cells and induction of host inflammatory responses. L-Arg availability is needed for talin-1 mRNA stability, and thus mediates the immunopathogenesis of C. rodentium infection.
Background and aim: Invasive, translocating bacteria inducing Th1 and Th17 responses are suspected to be at the origin of Crohn's disease (CD) in susceptible individuals with genetically determined innate immune defects. Ileal lesions of 36.4% of CD patients are colonized by pathogenic adherent-invasive Escherichia coli (AIEC), able to highly replicate in mature phagolysosomes within cultured macrophages. The aim of this study was to assess whether macrophages from CD patients showed impaired ability to control intracellular bacteria replication and pro-inflammatory cytokine expression in response to pathogenic AIEC or non-pathogenic E. coli infection. Methods: Human peripheral blood monocyte-derived macrophages were obtained from CD patients (n=26), ulcerative colitis (UC, n=5) patients and controls (n=16). All patients and controls were genotyped for the main coding mutations in NOD2 (SNP8, SNP12, and SNP13) and for ATG16L1 (rs2241880). Following in vitro infection with AIEC reference strain LF82 or non-pathogenic E. coli K-12 levels of intracellular bacteria at 1h and 10 h post-infection was assessed by using gentamicin protection assay. IL-6, IL-8, and tumour necrosis factor alpha (TNF-α) cytokine levels were evaluated at 10h post-infection by ELISA. Results: Significant differences between the levels of intracellular AIEC bacteria at 10 h post-infection were observed with macrophages from CD and UC patients or controls, the load of intracellular bacteria being higher in CD macrophages (ANOVA, p= 0.02). This was not observed when macrophages were infected with nonpathogenic E. coli. In our cohort of CD patients, only macrophages heterozygous for a NOD2 polymorphism were found and they did not show significant difference in their ability to control AIEC intracellular replication. Concerning ATG16L1 polymorphism, very high levels of intracellular AIEC bacteria were observed in AIEC-infected macrophages homozygous for ATG16L1 (T300A). The levels of TNF-α and IL-6 cytokine secreted were higher with AIEC-infected macrophages from CD patients compared to those of UC patients or controls (p=0.057 and 0.011, respectively) and significantly linked to the load of AIEC intracellular bacteria (p=0.018). Significant differences in IL-8 secretion levels were observed between AIEC-infected macrophages from UC and CD patients or controls (p=0.009). In contrast no significant difference in TNF-α, IL-6 or IL-8 secretion was observed between non pathogenic E. coli-infected macrophages from CD and UC patients or from controls. Conclusion: Human peripheral blood monocyte-derived macrophages from CD patients compared to those of UC patients or controls showed specific characteristics in response to AIEC infection but not to non-pathogenic E. coli challenge including load of intracellular bacteria and secretion of pro-inflammatory TNF-α and IL-6 cytokines.
Sa1747
Sa1749
Antimicrobial Peptide Cathelicidin Inhibits Salmonella Mediated Intestinal Inflammation and Fibrosis Samantha Ho, Kyriaki Bakirtzi, Richard E. Isaacson, Charalabos Pothoulakis, Hon Wai Koon
Investigating the Role of Interferon Regulatory Factor 8 in Helicobacter pyloriInduced Inflammatory Responses Ming Yan, Hongsheng Wang, Yin Zhu, Jungsoo Joo, Jiafang Sun, Chengfu Xu, Sun Yan, Herbert C. Morse, William G. Coleman
Background and Aims: Cathelicidin (LL-37 in human and mCRAMP in mice) is a family of endogenous anti-microbial peptides with anti-inflammatory effects. We previously discovered that intracolonic mouse cathelicidin (mCRAMP) peptide administration inhibited Clostridium difficile mediated colonic inflammation. Chronic Crohn's disease leads to intestinal inflammation and fibrosis (stricture). Salmonella infection model is similar to Crohn's disease in terms of Th1 and Th17 mechanisms, making it a relevant model to study colitis associated intestinal fibrosis (Grassl et al Gastroenterology 2008). Here we determined whether exogenous cathelicidin can modulate intestinal fibrosis in an animal model of intestinal inflammation. Methods: 129SvJ mice (n=6 per group) were pretreated with streptomycin orally followed by Salmonella typhimurium (strain SL1344) 3x10(8) cfu/100ul using oral gavage. Some mice received mouse cathelicidin expressing lentivirus (Camp-LV) 1x10(7) infectious units per mouse intravenously on day 11. Cecum is the main location of Salmonella induced inflammation and fibrosis. Cecal tissues were obtained on day 21 for analyses. Results: Chronic Salmonella infection induced cecal inflammation with fibrosis and stricture (7 fold increase in TNF mRNA p=0.0001 and 3.6 fold increase in collagen Col1a2 mRNA p=0.0005). The cecal inflammation and fibrosis were significantly reduced by mouse cathelicidin expressing lentivirus (40% reduction in TNF mRNA p=0.01 and 43% reduction in TNF mRNA p=0.02). Salmonella induced cecal endogenous cathelicidin expression (140 fold p=0.0001). Cathelicidin expressing lentivirus further increased cathelicidin expression to 268 fold (p=0.03). Cathelicidin treatment reduced Salmonella induced cecal histological damages (60% reduction in histology score, p=0.0001) and collagen deposition (50% reduction in fibrosis score, p=0.0001) as observed by H&E staining and Masson Trichrome staining. Cathelicidin treatment did not affect transforming growth factor beta 1 and vimentin (fibroblasts marker) mRNA expression in the cecum, suggesting that cathelicidin directly inhibited collagen expression without affecting fibroblast migration processes and viability in the tissues. Conclusion: Lentiviral administration of mouse cathelicidin modulates Salmonella induced intestinal inflammation and fibrosis in mice. Cathelicidin may be a future therapeutic approach against inflammatory bowel disease and its associated intestinal fibrosis. Supported by a Pilot and Feasibility Study grant from UCLA-CURE Center, Career Development Award from Crohn's and Colitis Foundation of America (#2691), K01DK084256 from National Institute of Health to HWK and Student research fellowship from Crohn's and Colitis Foundation of America to SH (#3831). Cathelicidin expressing lentivirus particles were prepared by UCLA Vector Core.
Interferon Regulatory Factor 8 (IRF8), also known as ICSBP (interferon consensus sequence binding protein), is a transcription factor of the interferon regulatory factor (IRF) family and has many functions involved in the regulation of development, growth and host defense in hematopoietic lineage cells including innate and adaptive immune responses. However, expression and function of IRF8 in non-hematopoietic cells remain poorly understood. Our microarray analysis showed that the IRF8 gene was differentially expressed in the gastric mucosa of Helicobacter pylori infected mice. The up-regulated expression levels of IRF8 mRNA expression and IRF8 protein were confirmed in the gastric epithelial cell line (GSM06), macrophage cell line (RAW264.7) and mice stomach tissues after H. pylori infection, by quantitative PCR and Western Blot. Then, we generated IRF8-EGFP fusion protein reporter mice (IRF8-EGFP mice) which allowed us to follow IRF8-EGFP expression in all cells and to monitor IRF8 expression during H. pylori infection. We found that IRF8 could express in gastric epithelial cells from IRF8-EGFP mouse stomach, mostly localized in the nucleus, while the fluorescence of IRF8 increased in gastric epithelial cells after H. pylori infection. Furthermore, IRF8-/- mice were used to investigate the potential role of IRF8 in gastric mucosal responses to H. pylori infection. H. pylori colonization in the gastric mucosa of IRF8-/- mice was significantly higher compared with wild-type littermates. Together these observations indicate : 1) IRF8 is expressed by gastric cells and its expression is increased following infection with H. pylori probably reflecting increased levels of IFNg ; 2) IRF8deficient mice have higher bacteria loads than normal controls, suggesting that IRF8 exerts a positive regulatory role in gastric mucosal innate immunity. Therefore, IRF8 is required for gastric mucosal innate immunity against infection with H. pylori. Sa1750 Olfactomedin 4 Deletion Enhances Host Pro-Inflammatory Immune Responses Against Helicobacter pylori Infection Through a MyD88 Dependent Mechanism Ming Yan, Wenli Liu, Chengfu Xu, Jungsoo Joo, Chaohui Yu, Yin Zhu, Sun Yan, Griffin Rodgers, William G. Coleman Olfactomedin 4 (OLFM4) is a novel anti-inflammatory mediator in H. pylori infection, which plays an important role in the regulation of host resistance and gastric inflammatory response to H. pylori infection. Our previous study showed that OLFM4 deletion enhances host proinflammatory immune responses against H. pylori infection in mice. However, the mechanism of its role in biological processes such as inflammation or other immune response is uncertain. In this study, we provide evidence that MyD88, a critical adaptor protein in innate immunity signal transduction, is involved in the regulatory network of OLFM4. Firstly, we observed that OLFM4 knockout significantly up-regulated MyD88 expression in gastric mucosa of H. pylori infected mice. Secondly, MyD88 and OLFM4 double knockout attenuated the alterations observed in OLFM4 knockout mice. In OLFM4 knockout mice, gastric H. pylori
S-287
AGA Abstracts
AGA Abstracts
Sa1746
Cationic Amino Acid Transporter 2 and L-Arginine Availability Are Required for Talin-1-Dependent Adherence of the Colonic Pathogen Citrobacter Rodentium and Subsequent Pro-Inflammatory Responses Kshipra Singh, Lori A. Coburn, Jennifer P. Druce, Mohammad Asim, Daniel P. Barry, Rupesh Chaturvedi, Keith T. Wilson
Comparative Behaviour of Macrophages Isolated From Patients With Crohn's Disease or Ulcerative Colitis and Controls in Response to Adherent-Invasive or Non-Pathogenic E. Coli Infection Emilie Vazeille, Anthony Buisson, Marion Goutte, Lemlih Ouchchane, Jean-Pierre Hugot, Amélie de Vallée, Gilles Bommelaer, Arlette Darfeuille-Michaud
Background: L-arginine (L-Arg) uptake in cells is mediated by cationic amino acid transporter (CAT) proteins, and CAT2 is the inducible form. We have found that CAT2-/- mice exhibit less colitis in the IBD model induced by infection with Citrobacter rodentium, a rodent pathogen similar to EPEC that acts by forming attaching and effacing lesions on epithelial cells. The translocated intimin receptor is injected into host cells by C. rodentium and forms a complex with talin-1 that mediates bacterial binding and downstream signaling. Our aim was to investigate the role of talin-1 in C. rodentium infection. Methods: Male C57BL/6 wild-type (WT) or CAT2-/- mice were infected with C. rodentium for 14 days. Talin-1 and the C. rodentium protein espB were assesed by confocal microscopy and Western blotting. mRNA levels of talin-1 and the proinflammatory CXC chemokines, KC and MIP-2, were determined by qPCR. Young adult mouse colon (YAMC) cells were transduced with control or talin-1 shRNA, and activated with C. rodentium at an MOI of 200. Bacterial adherence was assessed by culture after saponin treatment of cells. Levels of the NF-κB subunit p65 were assessed by immunofluorescence at 30 min, and of talin-1, KC and MIP-2 by qPCR at 4 h. Talin-1 mRNA stability was assessed in YAMC cells using the transcriptional inhibitor actinomycin D followed by serial assessment of mRNA levels. Results: C. rodentium infection in vivo induced a 4-fold increase in talin-1 mRNA and protein expression in whole tissues and a 236-fold increase in mRNA levels in colonic epithelial cells (CECs). Talin-1 and espB protein levels were markedly decreased in colon tissues from infected CAT2-/- vs. WT mice; this was confirmed by confocal microscopy and there was also less colocalization of these proteins. Talin-1, KC and MIP-2 mRNA levels were each decreased by >92% in CAT2-/- vs. WT mice (p<0.01). L-lysine, a competitive inhibitor of L-Arg uptake, reduced induction of talin-1, KC, and MIP-2 mRNA expression by 60.4 ± 18.3%, 91.7 ± 2.6%, and 68.9 ± 12.2%, respectively, in YAMC cells (p<0.01). In talin-1 knockdown cells, levels of adherent C. rodentium decreased from 4.9 ± 0.9 to 0.8 ± 0.2 bacteria/cell (p<0.05), and there was less nuclear translocation of p65. Similarly, KC and MIP-2 levels were decreased by 90.6 ± 0.3% and 92.5 ± 3.1%, respectively, in knockdown cells (p<0.01). There was a 4.2 ± 0.5-fold increase in talin-1 mRNA levels when cells starved of L-Arg were repleted with L-Arg for 4 h. Talin-1 mRNA was less stable in the absence of L-Arg; the mRNA half-life was 5.2fold (p<0.01) greater in cells repleted with L-Arg. Conclusions: Talin-1 is essential for C. rodentium adherence to colonic epithelial cells and induction of host inflammatory responses. L-Arg availability is needed for talin-1 mRNA stability, and thus mediates the immunopathogenesis of C. rodentium infection.
Background and aim: Invasive, translocating bacteria inducing Th1 and Th17 responses are suspected to be at the origin of Crohn's disease (CD) in susceptible individuals with genetically determined innate immune defects. Ileal lesions of 36.4% of CD patients are colonized by pathogenic adherent-invasive Escherichia coli (AIEC), able to highly replicate in mature phagolysosomes within cultured macrophages. The aim of this study was to assess whether macrophages from CD patients showed impaired ability to control intracellular bacteria replication and pro-inflammatory cytokine expression in response to pathogenic AIEC or non-pathogenic E. coli infection. Methods: Human peripheral blood monocyte-derived macrophages were obtained from CD patients (n=26), ulcerative colitis (UC, n=5) patients and controls (n=16). All patients and controls were genotyped for the main coding mutations in NOD2 (SNP8, SNP12, and SNP13) and for ATG16L1 (rs2241880). Following in vitro infection with AIEC reference strain LF82 or non-pathogenic E. coli K-12 levels of intracellular bacteria at 1h and 10 h post-infection was assessed by using gentamicin protection assay. IL-6, IL-8, and tumour necrosis factor alpha (TNF-α) cytokine levels were evaluated at 10h post-infection by ELISA. Results: Significant differences between the levels of intracellular AIEC bacteria at 10 h post-infection were observed with macrophages from CD and UC patients or controls, the load of intracellular bacteria being higher in CD macrophages (ANOVA, p= 0.02). This was not observed when macrophages were infected with nonpathogenic E. coli. In our cohort of CD patients, only macrophages heterozygous for a NOD2 polymorphism were found and they did not show significant difference in their ability to control AIEC intracellular replication. Concerning ATG16L1 polymorphism, very high levels of intracellular AIEC bacteria were observed in AIEC-infected macrophages homozygous for ATG16L1 (T300A). The levels of TNF-α and IL-6 cytokine secreted were higher with AIEC-infected macrophages from CD patients compared to those of UC patients or controls (p=0.057 and 0.011, respectively) and significantly linked to the load of AIEC intracellular bacteria (p=0.018). Significant differences in IL-8 secretion levels were observed between AIEC-infected macrophages from UC and CD patients or controls (p=0.009). In contrast no significant difference in TNF-α, IL-6 or IL-8 secretion was observed between non pathogenic E. coli-infected macrophages from CD and UC patients or from controls. Conclusion: Human peripheral blood monocyte-derived macrophages from CD patients compared to those of UC patients or controls showed specific characteristics in response to AIEC infection but not to non-pathogenic E. coli challenge including load of intracellular bacteria and secretion of pro-inflammatory TNF-α and IL-6 cytokines.
Sa1747
Sa1749
Antimicrobial Peptide Cathelicidin Inhibits Salmonella Mediated Intestinal Inflammation and Fibrosis Samantha Ho, Kyriaki Bakirtzi, Richard E. Isaacson, Charalabos Pothoulakis, Hon Wai Koon
Investigating the Role of Interferon Regulatory Factor 8 in Helicobacter pyloriInduced Inflammatory Responses Ming Yan, Hongsheng Wang, Yin Zhu, Jungsoo Joo, Jiafang Sun, Chengfu Xu, Sun Yan, Herbert C. Morse, William G. Coleman
Background and Aims: Cathelicidin (LL-37 in human and mCRAMP in mice) is a family of endogenous anti-microbial peptides with anti-inflammatory effects. We previously discovered that intracolonic mouse cathelicidin (mCRAMP) peptide administration inhibited Clostridium difficile mediated colonic inflammation. Chronic Crohn's disease leads to intestinal inflammation and fibrosis (stricture). Salmonella infection model is similar to Crohn's disease in terms of Th1 and Th17 mechanisms, making it a relevant model to study colitis associated intestinal fibrosis (Grassl et al Gastroenterology 2008). Here we determined whether exogenous cathelicidin can modulate intestinal fibrosis in an animal model of intestinal inflammation. Methods: 129SvJ mice (n=6 per group) were pretreated with streptomycin orally followed by Salmonella typhimurium (strain SL1344) 3x10(8) cfu/100ul using oral gavage. Some mice received mouse cathelicidin expressing lentivirus (Camp-LV) 1x10(7) infectious units per mouse intravenously on day 11. Cecum is the main location of Salmonella induced inflammation and fibrosis. Cecal tissues were obtained on day 21 for analyses. Results: Chronic Salmonella infection induced cecal inflammation with fibrosis and stricture (7 fold increase in TNF mRNA p=0.0001 and 3.6 fold increase in collagen Col1a2 mRNA p=0.0005). The cecal inflammation and fibrosis were significantly reduced by mouse cathelicidin expressing lentivirus (40% reduction in TNF mRNA p=0.01 and 43% reduction in TNF mRNA p=0.02). Salmonella induced cecal endogenous cathelicidin expression (140 fold p=0.0001). Cathelicidin expressing lentivirus further increased cathelicidin expression to 268 fold (p=0.03). Cathelicidin treatment reduced Salmonella induced cecal histological damages (60% reduction in histology score, p=0.0001) and collagen deposition (50% reduction in fibrosis score, p=0.0001) as observed by H&E staining and Masson Trichrome staining. Cathelicidin treatment did not affect transforming growth factor beta 1 and vimentin (fibroblasts marker) mRNA expression in the cecum, suggesting that cathelicidin directly inhibited collagen expression without affecting fibroblast migration processes and viability in the tissues. Conclusion: Lentiviral administration of mouse cathelicidin modulates Salmonella induced intestinal inflammation and fibrosis in mice. Cathelicidin may be a future therapeutic approach against inflammatory bowel disease and its associated intestinal fibrosis. Supported by a Pilot and Feasibility Study grant from UCLA-CURE Center, Career Development Award from Crohn's and Colitis Foundation of America (#2691), K01DK084256 from National Institute of Health to HWK and Student research fellowship from Crohn's and Colitis Foundation of America to SH (#3831). Cathelicidin expressing lentivirus particles were prepared by UCLA Vector Core.
Interferon Regulatory Factor 8 (IRF8), also known as ICSBP (interferon consensus sequence binding protein), is a transcription factor of the interferon regulatory factor (IRF) family and has many functions involved in the regulation of development, growth and host defense in hematopoietic lineage cells including innate and adaptive immune responses. However, expression and function of IRF8 in non-hematopoietic cells remain poorly understood. Our microarray analysis showed that the IRF8 gene was differentially expressed in the gastric mucosa of Helicobacter pylori infected mice. The up-regulated expression levels of IRF8 mRNA expression and IRF8 protein were confirmed in the gastric epithelial cell line (GSM06), macrophage cell line (RAW264.7) and mice stomach tissues after H. pylori infection, by quantitative PCR and Western Blot. Then, we generated IRF8-EGFP fusion protein reporter mice (IRF8-EGFP mice) which allowed us to follow IRF8-EGFP expression in all cells and to monitor IRF8 expression during H. pylori infection. We found that IRF8 could express in gastric epithelial cells from IRF8-EGFP mouse stomach, mostly localized in the nucleus, while the fluorescence of IRF8 increased in gastric epithelial cells after H. pylori infection. Furthermore, IRF8-/- mice were used to investigate the potential role of IRF8 in gastric mucosal responses to H. pylori infection. H. pylori colonization in the gastric mucosa of IRF8-/- mice was significantly higher compared with wild-type littermates. Together these observations indicate : 1) IRF8 is expressed by gastric cells and its expression is increased following infection with H. pylori probably reflecting increased levels of IFNg ; 2) IRF8deficient mice have higher bacteria loads than normal controls, suggesting that IRF8 exerts a positive regulatory role in gastric mucosal innate immunity. Therefore, IRF8 is required for gastric mucosal innate immunity against infection with H. pylori. Sa1750 Olfactomedin 4 Deletion Enhances Host Pro-Inflammatory Immune Responses Against Helicobacter pylori Infection Through a MyD88 Dependent Mechanism Ming Yan, Wenli Liu, Chengfu Xu, Jungsoo Joo, Chaohui Yu, Yin Zhu, Sun Yan, Griffin Rodgers, William G. Coleman Olfactomedin 4 (OLFM4) is a novel anti-inflammatory mediator in H. pylori infection, which plays an important role in the regulation of host resistance and gastric inflammatory response to H. pylori infection. Our previous study showed that OLFM4 deletion enhances host proinflammatory immune responses against H. pylori infection in mice. However, the mechanism of its role in biological processes such as inflammation or other immune response is uncertain. In this study, we provide evidence that MyD88, a critical adaptor protein in innate immunity signal transduction, is involved in the regulatory network of OLFM4. Firstly, we observed that OLFM4 knockout significantly up-regulated MyD88 expression in gastric mucosa of H. pylori infected mice. Secondly, MyD88 and OLFM4 double knockout attenuated the alterations observed in OLFM4 knockout mice. In OLFM4 knockout mice, gastric H. pylori
S-287
AGA Abstracts
AGA Abstracts
Sa1746