Interleukin-32 (IL-32), a multiple proinflammatory cytokine, plays a vital role in immune-related diseases and infectious diseases. The promoter region of IL-32, which showed functional polymorphism, could regulate IL-32 expression. Although IL-32 rs28372698 polymorphism has been related to a lot of inflammatory diseases, the association of IL-32 rs28372698 polymorphism with a hepatic flare of chronic HBV infection has not been reported. In the present study, IL-32 rs28372698 polymorphism was genotyped in 104 chronic HBV carriers and 151 active chronic hepatitis B (CHB) patients. The frequency of IL-32 T/T genotype in patients with active CHB was significantly higher than that in chronic HBV carriers. Furthermore, the frequency of the T allele at IL-32 rs28372698 in active CHB patients was also higher than that in chronic HBV carriers. The serum level of IL-32 in active CHB patients was higher than that in chronic HBV carriers. Our results imply that IL-32 T/T polymorphism might be associated with a hepatic flare of chronic HBV infection.

Background Aerobic glycolysis and epidermal–mesenchymal transition (EMT) play key roles in the development of bladder cancer. This study aimed to investigate the function and the underlying mechanism of dihydropyrimidinase like 2 (DPYSL2) in bladder cancer progression. Methods The expression pattern of DPYSL2 in bladder cancer and the correlation of DPYSL2 expression with clinicopathological characteristics of bladder cancer patients were analyzed using the data from different databases and tissue microarray. Gain- and loss-of-function assays were performed to explore the role of DPYSL2 in bladder cancer progression in vitro and in mice. Proteomic analysis was performed to identify the interacting partner of DPYSL2 in bladder cancer cells. Findings The results showed that DPYSL2 expression was upregulated in bladder cancer tissue compared with adjacent normal bladder tissue and in more aggressive cancer stages compared with lower stages. DPYSL2 promoted malignant behavior of bladder cancer cells in vitro, as well as tumor growth and distant metastasis in mice. Mechanistically, DPYSL2 interacted with pyruvate kinase M2 (PKM2) and promoted the conversion of PKM2 tetramers to PKM2 dimers. Knockdown of PKM2 completely blocked DPYSL2-induced enhancement of the malignant behavior, glucose uptake, lactic acid production, and epithelial–mesenchymal transition in bladder cancer cells. Interpretation In conclusion, the results suggest that DPYSL2 promotes aerobic glycolysis and EMT in bladder cancer via PKM2, serving as a potential therapeutic target for bladder cancer treatment.

Hepatic fibrosis is a necessarily stage from the progression of chronic liver diseases to cirrhosis, even hepatocellular carcinoma (HCC). Hepatic fibrosis is characterized by the progressive accumulation of extracellular matrix (ECM). The balance between ECM production and degradation is mediated by matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). TIMP-1 is an important regulator in the synthesis and degradation of ECM. IL-32, a multi-function cytokine, could induce IL-1β, IL-6, IL-8 and other cytokine expressions by activating AP-1, NF-κβ, p38MAPK signal pathways. IL-32 expression is increased in liver tissues of hepatic fibrosis. However, the role of IL-32 in the pathogenesis of liver fibrosis is not thoroughly clear. Recently, it is demonstrated that TIMP-1 expression is induced by the activation of AP-1 signal pathway. So we assayed the effect of IL-32 on TIMP-1 expression by LX-2 cells (one of HSCs cell lines) in the present study. We found that IL-32 could induce TIMP-1 expression by LX-2 cells at a dose-dependent manner. IL-32 could increase TIMP-1 promoter activity and induce TIMP-1 expression by activating AP-1 signal pathway. Moreover, the increase of TIMP-1 expression could promote the migration of LX-2 cells. In conclusion, we believe that IL-32 might be involved in the pathogenesis of hepatic fibrosis by inducing TIMP-1 expression.