A novel role for interleukin 32 in cholestasis

Furthermore, the results of serum biochemistry tests were in agreement with the above observations (Table S2). [...]the levels of hepatic BA and 7-α-C4 were significantly lower in the hIL32γLTg-BDL mice than in the WT-BDL mice (Table S2), indicating that hepatic IL32 represses BA synthesis. [...]RT-qPCR analysis revealed that hepatic mRNA levels of chemokines Cxcl5, Cxcl10 and Ccl2, as well as their receptors Cxcr2, Cxcr3 and Ccr2, were markedly decreased in hIL32γLTg-BDL mice compared with WT-BDL mice (Figures S6D,E and S8A-C). [...]these effects were diminished in the presence of Anisomycin, an agonist of JNK/MAPK signaling (Figure 3E). [...]ChIP qPCR assays demonstrated that the binding activities of c-Jun to the Cxcl5, Cxcl10 or Ccl2 promoters (c-Jun ChIP3 site located Cxcl5 -924 to -918, ChIP4 Cxcl10 -765 to -759 and ChIP6 Ccl2 -21 to -15) were significantly decreased in the liver tissues of hIL32γLTg-BDL mice compared to WT-BDL mice (Figure 3F and Figure S9B,C). [...]RT-qPCR, Sirius Red, Masson Trichrome, H&E staining and IHC labeling of CK19 analyses revealed that overexpression of IL32 also could be beneficial for the treatment of cholestatic liver fibrosis (Figures S12C and S15).