Rabbit Anti-Human IL22 Polyclonal Antibody

Benzotriazole ultraviolet stabilizers (BUVSs) are widely used additives in industrial materials and personal care products that protect products from ultraviolet damage. Due to their high production volume and potential to bioaccumulate, BUVSs are an environmental pollutant of concern. In this study, juvenile zebrafish (Danio rerio) were exposed to 4 BUVSs (UV-234, UV-326, UV-329, and UV-P) at 10 and 100 mg/L for 28 d. BUVSs induced hepatic vacuolization and nuclei pyknosis in the liver following 100 mg/L UV-234 and UV-329 exposure. Transcriptomic analysis in the liver uncovered pathways related to inflammation that were affected by BUVSs. Based upon these data, we measured the expression levels of 9 genes involved in AHR-IL17/IL22 pathway in zebrafish larvae exposed to each BUVSs at one dose of either 10 or 100 mg/L for 6 days in a second set experiment. Transcript levels of interleukins il17a and il22 were decreased, while il6 mRNA was increased with exposure to UV-234, UV-329, and UV-P. No change to targeted transcripts was observed with UV-326 treatments. Moreover, cyp1a1 and ahr2 levels were increased in larvae treated with 100 mg/L UV-329 or UV-P. Consistent with expression data, protein abundance of IL22 was decreased by 29% with exposure to 100 mg/L UV-P. Taken together, these results demonstrate that exposure to different benzotriazole congeners may be associated with immunotoxicity in zebrafish through the AHR-IL17/IL22 pathway, and this may be associated with hepatic damage with prolonged exposures. This study provides new insight into unique pathways perturbed by specific BUVSs congeners. (C) 2020 Elsevier Ltd. All rights reserved.

Interleukin (IL)-22 acts on epithelia, hepatocytes, and pancreatic cells and stimulates innate immunity, tissue protection, and repair. IL-22 may also cause inflammation and abnormal cell proliferation. The binding of IL-22 to its receptor is competed by IL-22 binding protein (IL-22BP), which may limit the deleterious effects of IL-22. The role of IL-22 and IL-22BP in chronic liver diseases is unknown. We addressed this question in individuals chronically infected with schistosomes or hepatitis C virus (HCV). We first demonstrate that schistosome eggs stimulate production of IL-22 transcripts and inhibit accumulation of IL22-BP transcripts in schistosome-infected mice, and that schistosome eggs selectively stimulate production of IL-22 in cultures of blood leukocytes from individuals chronically infected with Schistosoma japonicum. High IL-22 levels in cultures correlated with protection against hepatic fibrosis and portal hypertension. To test further the implication of IL-22/IL-22BP in hepatic disease, we analyzed common genetic variants of IL22RA2, which encodes IL-22BP, and found that the genotypes, AA, GG of rs6570136 (P=0.003; odds ratio [OR]=2), and CC, TT of rs2064501 (P=0.01; OR=2), were associated with severe fibrosis in Chinese infected with S. japonicum. We confirmed this result in Sudanese (rs6570136 GG [P=0.0007; OR=8.2], rs2064501 TT [P=0.02; OR=3.1]), and Brazilians (rs6570136 GG [P=0.003; OR=26], rs2064501 TC, TT (P=0.03; OR=11]) infected with S. mansoni. The aggravating genotypes were associated with high IL22RA2 transcripts levels. Furthermore, these same variants were also associated with HCV-induced fibrosis and cirrhosis (rs6570136 GG, GA [P=0.007; OR=1.7], rs2064501 TT, TC (P=0.004; OR=2.4]). Conclusions: These results provide strong evidence that IL-22 protects against and IL-22BP aggravates liver fibrosis and cirrhosis in humans with chronic liver infections. Thus, pharmacological modulation of IL-22 BP may be an effective strategy to limit cirrhosis. (Hepatology 2015;61:1321-1331)