title: Impaired dendritic cell maturation and IL-10 production following H. pylori stimulation in gastric cancer patients.
abstract: The current study was to investigate the interaction between Helicobacter pylori and human dendritic cells (DCs). Whether impaired DC function can influence the outcome of H. pylori infections. Human monocyte-derived DCs (MDDCs) from five gastric cancer patients and nine healthy controls were stimulated with H. pylori. Maturation markers of MDDC were examined by flow cytometry. IL-10 and TNF-α released by MDDCs and IL-17 produced by T cells were measured by ELISA. Regulatory signaling pathways of IL-10 were examined by ELISA, western blotting, and chromatin immunoprecipitation assay. The results showed that as compared with healthy individuals, the maturation marker CD40 in MDDCs, IL-17A expression from T cells, and IL-10 expression from MDDCs were significantly lower in gastric cancer patients. Blocking DC-SIGN, TLR2, and TLR4 could reverse H. pylori-associated IL-10 production. Activation of the p38 MAPK and NF-kB signaling pathways concomitant with decreased tri-methylated H3K9 and increased acetylated H3 accounted for the effect of H. pylori on IL-10 expression. Furthermore, upregulated IL-10 expression was significantly suppressed in H. pylori-pulsed MDDCs by histone acetyltransferase and methyltransferase inhibitors. Taken together, impaired DC function contributes to the less effective innate and adaptive immune responses against H. pylori seen in gastric cancer patients. H. pylori can regulate IL-10 production through Toll-like and DC-SIGN receptors, activates p-p38 MAPK signaling and the transcription factors NF-kB, and modulates histone modification.
authors.affiliation: Department of Microbiology, Kaohsiung Medical University, 100 Shih-Chuan 1st Road, Kaohsiung 807, Taiwan. m725006@kmu.edu.tw
authors.forename: Lin-Li
authors.initials: LL
authors.lastname: Chang
authors.forename: Sheng-Wen
authors.initials: SW
authors.lastname: Wang
authors.forename: I-Chen
authors.initials: IC
authors.lastname: Wu
authors.forename: Fang-Jung
authors.initials: FJ
authors.lastname: Yu
authors.forename: Yu-Chung
authors.initials: YC
authors.lastname: Su
authors.forename: Ye-Pin
authors.initials: YP
authors.lastname: Chen
authors.forename: Deng-Chyang
authors.initials: DC
authors.lastname: Wu
authors.forename: Chang-Hung
authors.initials: CH
authors.lastname: Kuo
authors.forename: Chih-Hsing
authors.initials: CH
authors.lastname: Hung
mesh_terms: D015153:Blotting, Western; D019013:CD40 Antigens / Q000032:analysis; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000737:chemistry / Q000276:immunology* / Q000382:microbiology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D016480:Helicobacter pylori / Q000276:immunology*; D006801:Humans; D047468:Immunoprecipitation; D016753:Interleukin-10 / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000276:immunology* / Q000382:microbiology*
chemical_list: D019013:CD40 Antigens; C508609:IL10 protein, human; D016753:Interleukin-10