Association of IL-17A/F polymorphisms with the risk of gastritis and gastric cancer in the Korean population
MOLECULAR & CELLULAR TOXICOLOGY
Authors: Choi, Won Suk; Kim, Olga; Yoon, Jung Hwan; Park, Yong Gyu; Nam, Suk Woo; Lee, Jung Young; Park, Won Sang
Abstract
We investigated the effects of IL-17A rs2275913 and IL-17F rs763780 polymorphisms on IL-17 expression and the association of these polymorphisms with the risk of gastritis and gastric cancer. IL-17A expression was closely associated with the degree of gastritis in 55 non-neoplastic gastric mucosae and was markedly decreased in subjects carrying A allele. In addition, IL-17F expression was increased in the T allele carriers, but was not associated with gastritis. In 300 gastric cancer patients, the frequency of the rs2275913 A/A genotype was significantly higher in intestinal-type gastric cancer, when compared to that of diffuse-type gastric cancer (P>0.05). There was a significant difference in genotype distribution and allele frequencies of IL-17F rs763780 when comparing gastric cancer patients and 247 healthy controls. These results suggest that the polymorphisms of IL-17F rs763780 and IL-17A rs2275913 are closely associated with susceptibility to the development of gastritis and gastric cancer in the Korean population.
HMGB1-TLR4-IL23-IL17A axis promotes paraquat-induced acute lung injury by mediating neutrophil infiltration in mice
SCIENTIFIC REPORTS
Authors: Yan, Bailing; Chen, Feng; Xu, Lijun; Xing, Jihong; Wang, Xuefu
Abstract
Paraquat is a poisoning herbicide that primarily targets lung, leading to severe acute lung injury characterized by extensive neutrophil infiltration. However, the mechanisms underlying the neutrophil infiltration is not clear. In this study, we demonstrated the significance of the signaling cascade from high-mobility group box 1 (HMGB1), to Toll-like receptor 4 (TLR4), interleukin-23 (IL-23), and lastly to IL-17A during the paraquat-induced neutrophil infiltration and the subsequent lung injury in mice. Paraquat challenge significantly elevated serum levels of IL-17A and IL-23, the percentage of IL-17A producing gamma delta T cells in the lung, and the level of HMGB1 in bronchoalveolar lavage fluid. Reducing IL-17A production using an anti-gamma delta T antibody, targeting IL-23 with the neutralizing antibody against IL-23p19, and blocking HMGB1 signaling by using glycyrrhizin or TLR4(-/-) mice all dramatically inhibited the infiltration of neutrophils and attenuated lung injury. These novel findings not only reveal the critical role of HMGB1-TLR4-IL-23-IL-17A axis in the pathogenesis of paraquat-induced acute lung injury, but also provide promising therapeutic targets for treating paraquat poisoning.