Cytokine gene polymorphisms influence mucosal cytokine expression, gastric inflammation, and host specific colonisation during Helicobacter pylori infection

Rod, R.; Dossumbekova, A.; Neu, B.; Lang, R.; Bauer, S.; Saur, D.; Gerhard, M.; Prinz, C.
August 2004
Gut;Aug2004, Vol. 53 Issue 8, p1082
Academic Journal
Background and aims: Recent studies linked cytokine gene polymorphisms to H pylon related gastric cancer development. The current study evaluated the role of cytokine gene polymorphisms for mucosal cytokine expression, the gastric inflammatory response, and bacterial colonisation during H pylon infection. Patients and methods: In 207 H pylon infected patients with chronic gastritis, polymorphisms at different loci of the interleukin (1L)- 10, 1L- 1B, 1L-1 receptor antagonist (1L- 1RN), tumour necrosis factor (TNF)-A, and interferon (IFN)-G genes were genotyped by polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP) analysis, and allelic discriminating TaqMan PCR. Mucosal cytokine mRNA copy numbers were determined by real time quantitative PCR. Presence of bacterial virulence factors was investigated by cagA, vacAs 1/2, and babA2 PCR. Biopsies were assessed with regard to the degrees of granulocytic/lymphocytic infiltration and the presence of intestinal metaplasia (IM) and atrophic gastritis (AG). Results: Proinflammatory IL-1 polymorphisms (IL-1RN*2+/IL-1B-511T/-31C) were associated with increased IL-1β expression, more severe degrees of inflammation, and an increased prevalence of IM and AG. Carriers of the 11-10-1082G/ -81 9C/ - 592C alleles (GCC haplolype) had higher mucosal IL-10 mRNA levels than ATA haplotype carriers and were associated with colonisation by more virulent cagA+ vac4s1+, and babA2+ H pylori strains. The TNF-A-307(G/A) and IFN-G+874(A/T) polymorphisms did not influence mucosal cytokine expression or the inflammatory response to H pylon. Conclusions: Cytokine gene polymorphisms influence mucosal cytokine expression, gastric inflammation, and the long term development of precancerous lesions in H pylon infection. Host polymorphisms are associated with certain bacterial strain types, suggesting host specific colonisation or adaptation. These findings contribute to the understanding of the complex interplay between host and bacterial factors involved in the development of gastric pathology.


Related Articles

  • Defining the Roles of IFN-γ and IL-17A in Inflammation and Protection against Helicobacter pylori Infection. Sjökvist Ottsjö, Louise; Flach, Carl-Fredrik; Nilsson, Staffan; de Waal Malefyt, Rene; Walduck, Anna K.; Raghavan, Sukanya // PLoS ONE;7/13/2015, Vol. 10 Issue 7, p1 

    CD4+ T cells have been shown to be essential for vaccine-induced protection against Helicobacter pylori infection. However, the effector mechanisms leading to reductions in the gastric bacterial loads of vaccinated mice remain unclear. We have investigated the function of IFN-γ and IL-17A for...

  • A2A adenosine receptor (AR) activation inhibits pro-inflammatory cytokine production by human CD4+ helper T cells and regulates Helicobacter-induced gastritis and bacterial persistence. Alam, M. S.; Kurtz, C. C.; Wilson, J. M.; Burnette, B. R.; Wiznerowicz, E. B.; Ross, W. G.; Rieger, J. M.; Figler, R. A.; Linden, J.; Crowe, S. E.; Ernst, P. B. // Mucosal Immunology (1933-0219);May2009, Vol. 2 Issue 3, p232 

    Helicobacter pylori causes a lifelong infection and provides a model of bacterial adaptation and persistent colonization. Adenosine is an anti-inflammatory mediator that limits tissue damage during inflammation. We studied the role of adenosine in the T-cell-mediated regulation of gastritis and...

  • Cytokine Promoter Polymorphisms in Severe Sepsis. Stüber, Frank; Klaschik, Sven; Lehmann, Lutz Eric; Schewe, Jens-Christian; Weber, Stefan; Book, Malte // Clinical Infectious Diseases;11/15/2005 Supplement, Vol. 41, pS416 

    The need to develop individualized risk profiles and drug therapy regimens motivates interest in genetic studies of critically ill patients. Gene promoter variants may predict interindividual variability in response to inflammatory stimuli, such as infection and trauma. Genomic variations also...

  • Interleukin-27 and IFNγ regulate the expression of CXCL9, CXCL10, and CXCL11 in hepatitis. Basset, Laëtitia; Chevalier, Sylvie; Danger, Yannic; Arshad, Muhammad; Piquet-Pellorce, Claire; Gascan, Hugues; Samson, Michel // Journal of Molecular Medicine;Dec2015, Vol. 93 Issue 12, p1355 

    Interleukin-27 (IL-27) belongs to the IL-6/IL-12 family of cytokines, associated with different inflammatory diseases and orchestrates its biological activity via common heterodimeric receptor composed of WSX-1 (IL-27Rα) and gp130. The present study was aimed to investigate the regulation of...

  • Gastric Cancer Susceptibility Is Not Linked to Pro-and Anti-Inflammatory Cytokine Gene Polymorphisms in Whites: A Nationwide Multicenter Study in Spain. García-González, María Asunción; Lanas, Angel; Quintero, Enrique; Nicolás, David; Parra-Blanco, Adolfo; Strunk, Mark; Benito, Rafael; Angel Simón, Miguel; Santolaria, Santos; Sopeña, Federico; Piazuelo, Elena; Jiménez, Pilar; Pascual, Cristina; Mas, Eva; Irún, Pilar; Espinel, Jesús; Campo, Rafael; Manzano, Marisa; Geijo, Fernando; Pellis, Maria // American Journal of Gastroenterology;Sep2007, Vol. 102 Issue 9, p1878 

    BACKGROUND AND AIMS: Recent studies have reported an association between cytokine gene polymorphisms and GC risk. However, results are inconsistent among studies from different geographic regions and ethnic groups. Our goal was to evaluate the influence of Helicobacter pylori ( H. pylori)...

  • Interleukin-8 Regulates Expression of Reg Protein in Helicobacter pylori-Infected Gastric Mucosa. Yoshino, Nagisa; Ishihara, Shunji; Rumi, M. A. K.; Ortega-Cava, C. F.; Yuki, Takafumi; Kazumori, Hideaki; Takazawa, Shin; Okamoto, Hiroshi; Kadowaki, Yasunori; Kinoshita, Yoshikazu // American Journal of Gastroenterology;Oct2005, Vol. 100 Issue 10, p2157 

    BACKGROUND & AIM: Chronic inflammation induced by Helicobacter pylori infection is closely associated with epithelial cell proliferation and apoptosis, which are related to cellular turnover in gastric mucosa. Reg protein is a regenerating gene product and a potent growth factor for gastric...

  • Concurrent Proinflammatory and Apoptotic Activity of a Helicobacter pylori Protein (HP986) Points to Its Role in Chronic Persistence. Alvi, Ayesha; Ansari, Suhail A.; Ehtesham, Nasreen Z.; Rizwan, Mohammed; Devi, Savita; Sechi, Leonardo A.; Qureshi, Insaf A.; Hasnain, Seyed E.; Ahmed, Niyaz // PLoS ONE;2011, Vol. 6 Issue 7, p1 

    Helicobacter pylori induces cytokine mediated changes in gastroduodenal pathophysiology, wherein, the activated macrophages at the sub-mucosal space play a central role in mounting innate immune response against the antigens. The bacterium gains niche through persistent inflammation and local...

  • Transcriptional profiling of gastric epithelial cells infected with wild type or arginase-deficient Helicobacter pylori. Kim, Songhee H.; Sierra, Rosa A.; McGee, David J.; Zabaleta, Jovanny // BMC Microbiology;2012, Vol. 12 Issue 1, p175 

    Background: Helicobacter pylori causes acute and chronic gastric inflammation induced by proinflammatory cytokines and chemokines secreted by cells of the gastric mucosa, including gastric epithelial cells. Previous studies have demonstrated that the bacterial arginase, RocF, is involved in...

  • The biological function of Helicobacter cystein-rich protein A (HcpA) is IL-12 dependent and located at the carboxyterminus. Aigner, M.; Decker, J.; Deml, L.; Knoll, G.; Lehn, N.; Schneider-Brachert, W. // Gut;Sep2002 Supplement 2, Vol. 51, pA21 

    Helicobacter cystein-rich protein A (HcpA) was recently shown by us to be capable of inducing high levels of interferon-γ (IFN-γ) from naive murine splenocytes. IFN-γ is the signature cytokine of the Th1 subset of helper T cells which are commonly held responsible for inflammatory...


Read the Article


Sign out of this library

Other Topics