Inhibition of IL-13 and IL-13Rα2 Expression by IL-32θ in Human Monocytic Cells Requires PKCδ and STAT3 Association.

Interleukin (IL)-32, a newly identified IL-32 isoform, has been reported to exert pro-inflammatory effects through the association with protein kinase C delta (PKC). In this study, we further examined the effects of IL-32 on IL-13 and IL-13R2 expression and the related mechanism in THP-1 cells. Upon stimulating IL-32-expressing and non-expressing cells with phorbol 12-myristate 13-acetate (PMA), the previous microarray analysis showed that IL-13R2 and IL-13 mRNA expression were significantly decreased by IL-32. The protein expression of these factors was also confirmed to be down-regulated. The nuclear translocation of transcription factors STAT3 and STAT6, which are necessary for IL-13R2 and IL-13 promoter activities, was suppressed by IL-32. Additionally, a direct association was found between IL-32, PKC, and signal transducer and activator of transcription 3 (STAT3), but not STAT6, revealing that IL-32 might act mainly through STAT3 and indirectly affect STAT6. Moreover, the interaction of IL-32 with STAT3 requires PKC, since blocking PKC activity eliminated the interaction and consequently limited the inhibitory effect of IL-32 on STAT3 activity. Interfering with STAT3 or STAT6 binding by decoy oligodeoxynucleotides (ODNs) identified that IL-32 had additive effects with the STAT3 decoy ODN to suppress IL-13 and IL-13R2 mRNA expression. Taken together, our data demonstrate the intracellular interaction of IL-32, PKC, and STAT3 to regulate IL-13 and IL-13R2 synthesis, supporting the role of IL-32 as an inflammatory modulator.