Helicobacter pylori Heat Shock Protein 60 Mediates Interleukin-6 Production by Macrophages via a Toll-like Receptor (TLR)-2-, TLR-4-, and Myeloid Differentiation Factor 88-independent Mechanism (original) (raw)
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Microbiology, 2004
Helicobacter pylori and gastric epithelial cells results in activation of NF-kB followed by secretion of interleukin (IL)-8. However, host-cell receptor(s) and their ligands involved in H. pylori-related IL-8 production have yet to be fully defined. In this study, the interaction between Toll-like receptors (TLRs), which are host receptors for pathogens involved in the innate immune response, and heat-shock protein (HSP) 60, an immune-potent antigen of H. pylori, was examined during H. pylori-induced IL-8 secretion in vitro. Recombinant H. pylori HSP60 (rHpHSP60) was prepared and added to cultured KATO III human gastric epithelial cells with or without pre-incubation with mouse monoclonal anti-TLR2 or anti-TLR4 antibodies. IL-8 mRNA expression and IL-8 protein release were analysed by Northern blotting and immunoassay. Involvement of NF-kB activation was analysed immunocytochemically by anti-NF-kB p65 antibody and ammonium pyrrolidinedithiocarbamate (PDTC), an inhibitor of NF-kB-mediated transcriptional activation. rHpHSP60 induced IL-8 mRNA expression and IL-8 secretion in a dose-dependent manner in KATO III cells. Anti-TLR2 antibody inhibited rHpHSP60-induced IL-8 secretion by 75 %, and anti-TLR4 antibody inhibited it by 30 %. rHpHSP60 induced nuclear translocation of NF-kB p65, which was inhibited by pretreatment with anti-TLR2 antibody. Treatment with PDTC significantly decreased the secretion of IL-8 induced by rHpHSP60. These findings suggest that H. pylori HSP60 activates NF-kB and induces IL-8 production through TLR-triggered pathways in gastric epithelial cells. Thus, it is possible that H. pylori HSP60 and TLR interaction in host cells contributes to the development of gastric inflammation caused by H. pylori infection.
Journal of Medical Microbiology, 2005
Interleukin 8 (IL8) is usually produced in both epithelial and monocytic cells during bacterial infections, causing inflammation. Helicobacter pylori induces production of IL8 from gastric epithelial cells via its cag pathogenicity island (cag PAI) system, LPS and outer-membrane protein. In some bacteria, heat-shock protein 60 (HSP60) also elicits a strong pro-inflammatory response in cells of the innate immune system. Three recombinant H. pylori HSP60 (rHSP60) proteins of different sizes were produced and one of these was used to raise two monoclonal antibodies (2E7 and 7B5). IL8 production was found to be induced in cultured monocytic cells treated with H. pylori cells or rHSP60 proteins, as measured by ELISA, and the amount of IL8 produced was dosedependent. Pre-incubation of H. pylori cells or rHSP60 preparations with the antibody 2E7 significantly inhibited IL8 production from monocytic cells. These results indicated that HSP60 is closely associated with IL8 production in monocytic cells.
FEMS Immunology and Medical Microbiology, 2001
Helicobacter pylori is a cause of chronic gastritis and leads to development of atrophy in some cases. There is evidence that the heat shock protein 60 (HSP60) of H. pylori is involved in induction of chronic inflammation. Seroprevalence of IgG antibodies to H. pylori HSP60 in an adult cohort from Saaremaa, Estonia (68 persons, median age 57 years), with a high prevalence of antibodies to cell surface proteins of H. pylori (92%) and a well characterized dynamics of chronic gastritis in an 18-year follow-up study, was tested using purified H. pylori HSP60 at a concentration of 1 Wg ml 31 with ELISA. The state of the gastric mucosa and the presence of H. pylori in histological sections in the samples of 1979 and 1997 were assessed in accordance with the Sydney system. Seropositivity for H. pylori HSP60 was 65%. Immunological response to H. pylori HSP60 is associated with the morphological presence of H. pylori in the antrum and corpus (P = 0.01) and is strongly correlated with the grade of chronic inflammation, particularly in the antrum mucosa (r = 0.34; P = 0.003; OR = 5.97 (95% CI 1.21^29.3)), but is not associated with development of atrophy during 18 years of follow-up, or with the activity of gastritis. This finding supports the evidence that immunological response to H. pylori HSP60 may play a role in triggering of the inflammatory process in the gastric mucosa. ß
Helicobacter Pylori HP0175 Promotes the Production of IL-23, IL-6, IL-1β and TGF-β
European Journal of Inflammation, 2013
Helicobacter pylori infection induces a chronic gastric inflammatory infiltrate. This study was undertaken to evaluate the type of the innate immune responses elicited by the secreted peptidyl-prolyl cis-trans isomerase of H. pylori (HP0175). The cytokine production induced by HP0175 in neutrophils, and monocytes was evaluated. HP0175 was able to induce the expression of IL-23 in neutrophils, and monocytes, and IL-6, IL-1beta and TGF-beta in monocytes. These findings indicate that HP0175 is able to promote the activation of innate cells and the production of a cytokine milieu that may favour the development of Th17 response.
Helicobacter pylori Activates Toll-Like Receptor 4 Expression in Gastrointestinal Epithelial Cells
Infection and Immunity, 2003
Helicobacter pylori activates the transcription factor NF-κB, leading to proinflammatory cytokine production by gastric epithelial cells. However, the receptors for the initial bacterial interaction with host cells which activate downstream signaling events have not been completely defined. Recently, it has been shown that microbial components activate Toll-like receptors (TLRs), thereby leading to AP-1- and NF-κB-dependent transcription and resulting in the production of proinflammatory cytokines. The aim of this study was to determine whether H. pylori activates TLR4. Reverse transcription-PCR showed that both type I and type II H. pylori clinical isolates induced TLR4 mRNA expression in AGS cells compared with that by uninfected controls. H. pylori upregulated TLR4 protein expression in two gastric epithelial cell lines (AGS and MKN45) and one intestinal epithelial cell line (T84). Monoclonal TLR4 antibody inhibited lipopolysaccharide-induced interleukin-8 secretion from THP-1 ma...
LOCAL CYTOKINE AND THE CD74 EXPRESSION IN THE HELICOBACTER PYLORI ASSOCIATED GASTRITIS
Nidhal R. Mahdi* Nidhal Abdul Mohaymen* * ABSTRACT: Helicobacter pylori infected gastric mucosa; the host immune response is unable to clear the infection and may contribute to the associated pathogenesis; CD74 expressed on the surface of gastric epithelial cells, as an adhesion molecules used by H. pylori that may contribute to the proinflammatory immune response seen during infection. This study aimed to investigate the role of local inflammatory cells infiltrating gastric mucosa that stained with IFN- and IL-6 monoclonal antibodies, as well as CD74 expressed on gastric epithelial cells in the immunopathogenic association with H. pylori gastritis. After the diagnosis of H. pylori infection by invasive and non-invasive diagnostic tests, patients were grouped as H. pylori positive, (n=47) and H. pylori negative (n=17). The immune staining of IL-6 and IFN- were positive at high level in 89.4% and 91.5%, respectively in H. pylori infected patients. In addition, the presence of specific stained lamina propria (MNCs and PMNs) cells with IL-6 and IFN- were significantly higher (P=0.0001) in the H. pylori-infected than in uninfected subjects; as well as a significant difference in the CD74 expression (p= 0.005) between infected and uninfected patients. It is concluded from this study that there was a significant difference between infected and uninfected biopsy specimens in the expression of CD74 in association with increase local presence of IFN- and IL-6, as well as PMNCs and MNCs, in the gastric mucosa. KEY WORDS: Helicobacter pylori; CD74; Immunohistochemistry (IHC); interleukin-6 (IL-6); gamma interferon ( IFN-); polymorphonuclear cells (PMNs); Mononuclear cells(MNCs) CORRESPONDENCE: Nidhal Raoof Mahdi* Dept. of Microbiology, College of Veterinary Medicine, University of Baghdad E-mail: dr.nidhalraoof @yahoo.com Nidhal abdul Mohaymen Dept. of Microbiology, College of Medicine, Al- Nahrain University ARTICLE CODE: 04.01.11
International Journal of Clinical & Laboratory Research, 1996
It is thought thatHelicobacter pylori colonization of the gastric mucosa might stimulate the production of several cytokines, which might trigger and maintain the gastric inflammation associated withHelicobacter pylori infection. In the present study we evaluated interleukin-1β, interleukin-6, and the soluble receptor of interleukin-2 both in mucosal homogenates and in the sera ofHelicobacter pylori-infected (39 cases) and uninfected (40 cases) patients to investigate whether there was any relationship between variations in cytokines and (1) the severity ofHelicobacter pylori-associated gastritis or (2) CagA-positiveHelicobacter pylori strains. Mucosal, but not serum levels of interleukins-1 and-6 and interleukin-2 receptor were significantly higher in infected than uninfected patients, Serum levels ofHelicobacter pylori antibodies were significantly higher in infected than uninfected patients, These levels correlated with mucosal interleukin-1β. The degree of antral or body inflammatory grade was higher in infected than in uninfected patients; cytokines levels were higher in patients with high-grade gastritis, most of whom wereHelicobacter pylori positive. Patients infected with CagA-positive strains also had higher levels of interleukin-1β, but not of interleukin-2 receptor or interleukin-6. In conclusion,Helicobacter pylori infection results in a local increase in interleukins-1β and-6 and interleukin-2 receptor associated with high-grade mucosal inflammation. Interleukin-1β seems to favor anti-Helicobacter pylori antibody production, and mucosal levels are enhanced mainly in patients infected with cytotoxicHelicobacter pylori strains.
Macrophages Are Mediators of Gastritis in Acute Helicobacter pylori Infection in C57BL/6 Mice
Infection and Immunity, 2008
Helicobacter pylori is the etiological agent of human chronic gastritis, a condition seen as a precursor to the development of gastrointestinal ulcers or gastric cancer. This study utilized the murine model of chronic H. pylori infection to characterize the role of macrophages in the induction of specific immune responses and gastritis and in the control of the bacterial burden following H. pylori infection and vaccination. Drug-loaded liposomes were injected intravenously to deplete macrophages from C57BL/6 mice, and effective removal of CD11b ؉ cells from the spleens and stomachs of mice was confirmed by immunofluorescence microscopy. Transient elimination of macrophages from C57BL/6 mice during the early period of infection reduced the gastric pathology induced by H. pylori SS1 but did not affect the bacterial load in the stomach. These data suggest that macrophages are important to the severity of gastric inflammation during H. pylori infection.
Gastroenterology, 1995
Background~Aims: Helicobacter pylori is associated with neutrophil infiltrates, although the mechanism of their recruitment is only partially defined. The aim of the study was to determine if Kato III, a human gastric epithelial cell line, expressed cytokines and the intercellular adhesion molecule 1 (ICAM-1), which could contribute to the initiation of inflammation during infection with H. pylori. Methods: Kato III cells were stimulated with H. pylori and were examined for evidence of infection, cytokine production, and the expression of ICAM-I. Results: The expression of interleukin 8 messenger RNA and immunoreactive protein by Kato III cells was significantly increased over constitutive levels within 3 hours of infection with H. pylori. Infected