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Inhibition of IL-13 and IL-13R?2 Expression by IL-32? in Human Monocytic Cells Requires PKC? and STAT3 Association.


ABSTRACT: 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-13R?2 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-13R?2 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-13R?2 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-13R?2 mRNA expression. Taken together, our data demonstrate the intracellular interaction of IL-32?, PKC?, and STAT3 to regulate IL-13 and IL-13R?2 synthesis, supporting the role of IL-32? as an inflammatory modulator.

PROVIDER: S-EPMC6514684 | BioStudies |

REPOSITORIES: biostudies

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