Dataset Information

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.

SUBMITTER: Pham TH

PROVIDER: S-EPMC6514684 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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

Pham Thu-Huyen TH Bak Yesol Y Oh Jae-Wook JW Hong Jingi J Lee Seungyeoun S Hong Jin Tae JT Yoon Do-Young DY

International journal of molecular sciences 20190420 8

Interleukin (IL)-32θ, a newly identified IL-32 isoform, has been reported to exert pro-inflammatory effects through the association with protein kinase C delta (PKCδ). In this study, we further examined the effects of IL-32θ on IL-13 and IL-13Rα2 expression and the related mechanism in THP-1 cells. Upon stimulating IL-32θ-expressing and non-expressing cells with phorbol 12-myristate 13-acetate (PMA), the previous microarray analysis showed that IL-13Rα2 and IL-13 mRNA expression were significant ...[more]

PMID: 31010051

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Project description:We have shown that manipulation of IL-13 and STAT6 signaling at the vaccination site can lead to different innate lymphoid cell (ILC)/dendritic cell (DC) recruitment, resulting in high avidity/poly-functional T cells and effective antibody differentiation. Here we show that permanent versus transient blockage of IL-13 and STAT6 at the vaccination site can lead to unique ILC-derived IL-13 and IFN-γ profiles, and differential IL-13Rα2, type I and II IL-4 receptor regulation on ILC. Specifically, STAT6-/- BALB/c mice given fowl pox virus (FPV) expressing HIV antigens induced elevated ST2/IL-33R+ ILC2-derived IL-13 and reduced NKp46+/- ILC1/ILC3-derived IFN-γ expression, whilst the opposite (reduced IL-13 and elevated IFN-γ expression) was observed during transient inhibition of STAT6 signaling in wild type BALB/c mice given FPV-HIV-IL-4R antagonist vaccination. Interestingly, disruption/inhibition of STAT6 signaling considerably impacted IL-13Rα2 expression by ST2/IL-33R+ ILC2 and NKp46- ILC1/ILC3, unlike direct IL-13 inhibition. Consistently with our previous findings, this further indicated that inhibition of STAT6 most likely promoted IL-13 regulation via IL-13Rα2. Moreover, the elevated ST2/IL-33R+ IL-13Rα2+ lung ILC2, 24 h post FPV-HIV-IL-4R antagonist vaccination was also suggestive of an autocrine regulation of ILC2-derived IL-13 and IL-13Rα2, under certain conditions. Knowing that IL-13 can modulate IFN-γ expression, the elevated expression of IFN-γR on lung ST2/IL-33R+ ILC2 provoked the notion that there could also be inter-regulation of lung ILC2-derived IL-13 and NKp46- ILC1/ILC3-derived IFN-γ via their respective receptors (IFN-γR and IL-13Rα2) at the lung mucosae early stages of vaccination. Intriguingly, under different IL-13 conditions differential regulation of IL-13/IL-13Rα2 on lung DC was also observed. Collectively these findings further substantiated that IL-13 is the master regulator of, not only DC, but also different ILC subsets at early stages of viral vector vaccination, and responsible for shaping the downstream adaptive immune outcomes. Thus, thoughtful selection of vaccine strategies/adjuvants that can manipulate IL-13Rα2, and STAT6 signaling at the ILC/DC level may prove useful in designing more efficacious vaccines against different/chronic pathogens.

Dataset Information

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

Publications

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

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