Aim: Our aim was to study the relationship between interleukin 1B (IL-1B) polymorphism, Helicobacter pylori infection, and gastric cancer in high prevalent (Shanxi) and low prevalent (Guangdong) regions in China. Method: Genomic DNA was extracted from peripheral blood of 192 healthy volunteers, 84 gastric cancer patients from Guangdong and 169 healthy volunteers, and 86 gastric cancer patients from Shanxi. Polymorphisms in IL-1B that encodes IL-1b and IL-1RN that encodes IL-1 receptor antagonist were analysed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). These polymorphic sites include promoter regions of IL-1B at positions +3954, 2511 (C-T transition), and 231 (T-C transition), and IL-1RN variable tandem repeats. Results: In the low prevalence region, the frequencies of the IL-1B +3954 T/T and IL-1RN *2/*2 genotypes were similar. IL-1B 2511T/T genotype frequency was significantly higher among patients with gastric cancer (25.0%) than control subjects (12.5%) (x 2 = 6.7, p = 0.01). In the high prevalence region, the frequencies of the IL-1B +3954T/T and 2511T/T genotypes and the IL-1RN *2/*2 genotype in the cancer and control groups were similar. IL-1B 231C/C genotype frequency was significantly higher among patients with gastric cancer (90.0%) than controls (78.0%) (x 2 = 5.0, p = 0.025). Compared with the low prevalence region, control subjects from the high prevalence region had a higher frequency of the IL-1B 2511T/T genotype (23.0% v 12.5%; x 2 = 7.0, p,0.008). While H pylori infection alone had only a modest effect on the risk of gastric cancer development (odds ratio (OR) 5.0 (95% confidence interval (CI) 1.5-16.3)), combined with the IL-1B 2511T/T genotype the risk was markedly elevated (OR 17.1, 95% CI 3.8-76.4). Conclusion: IL-1B 2511T/T genotypes are associated with gastric cancer in China. The effect of IL-1B polymorphism is less obvious in areas of high prevalence for gastric cancer.

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Toll-like receptor-3 (TLR3) priming may enhance mesenchymal stem cell (MSC) immunosuppressive activity, but this mechanism has not been investigated in the context of inflammatory bowel disease. Thus, we assessed the immunosuppressive properties of TLR3-primed MSCs using a trinitrobenzene sulfonate (TNBS)-induced mouse model of colitis. Intraperitoneally injected polyribocytidylic acid (poly (I:C)- (a ligand of TLR3) primed human umbilical cord-derived MSCs (hUC-MSCs) migrated to the inflamed colon and effectively improved clinical and pathological manifestations in colitic mice compared with mice treated with unstimulated hUC-MSCs (UCMs). Poly (I:C)-MSCs decreased a wide range of inflammatory cytokines and increased systemic interleukin-10 (IL-10) levels in colonic tissues. Poly (I:C)-MSCs also impaired T-helper type 1/17 (Th1/17) cell expansion and enhanced the suppressive effects of regulatory T cells (Treg) in vitro and in vivo. Poly (I:C)-MSCs suppressed the proliferation of activated mesenteric lymph node (MLN) cells via the overproduction of prostaglandin E (PGE) and upregulation of Jagged-1. PGE produced by hUC-MSCs in response to poly (I:C) increased the production of IL-10 and promoted the differentiation of Treg, which could be reversed by inhibition of Notch-1. Collectively, preconditioning MSCs with poly (I:C) enhanced the therapeutic effects of hUC-MSCs in TNBS-induced colitis, and TLR3-activated Notch-1 signaling regulated the immune suppression of hUC-MSCs through the production of PGE.

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