International Journal of Molecular Sciences Article Inhibition of IL-13 and IL-13Rα2 Expression by IL-32θ in Human Monocytic Cells Requires PKCδ and STAT3 Association Thu-Huyen Pham 1 , Yesol Bak 1 , Jae-Wook Oh 2 , Jingi Hong 3 , Seungyeoun Lee 3 , Jin Tae Hong 4, * and Do-Young Yoon 1, * 1 Department of Bioscience and Biotechnology, Konkuk University, Seoul 05029, Korea; huyenpham@konkuk.ac.kr (T.-H.P.); ysbak88@gmail.com (Y.B.) 2 Department of Stem cell and Regenerative Biotechnology, Konkuk University, Seoul 05029, Korea; ohjw@konkuk.ac.kr 3 Department of Mathematics and Statistics, Sejong University, Seoul 05006, Korea; wlsrl130@gmail.com (J.H.); leesy@sejong.ac.kr (S.L.) 4 College of Pharmacy and Medical Research Center, Chungbuk National University, Chungbuk 28160, Korea * Correspondence: jinthong@chungbuk.ac.kr (J.T.H.); ydy4218@konkuk.ac.kr (D.-Y.Y.) Received: 17 February 2019; Accepted: 19 April 2019; Published: 20 April 2019   Abstract: 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 significantly decreased by IL-32θ. 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-13Rα2 and IL-13 promoter activities, was suppressed by IL-32θ. Additionally, a direct association was found between IL-32θ, PKCδ, and signal transducer and activator of transcription 3 (STAT3), but not STAT6, revealing that IL-32θ might act mainly through STAT3 and indirectly affect STAT6. Moreover, the interaction of IL-32θ with STAT3 requires PKCδ, since blocking PKCδ activity eliminated the interaction and consequently limited the inhibitory effect of IL-32θ on STAT3 activity. Interfering with STAT3 or STAT6 binding by decoy oligodeoxynucleotides (ODNs) identified that IL-32θ had additive effects with the STAT3 decoy ODN to suppress IL-13 and IL-13Rα2 mRNA expression. Taken together, our data demonstrate the intracellular interaction of IL-32θ, PKCδ, and STAT3 to regulate IL-13 and IL-13Rα2 synthesis, supporting the role of IL-32θ as an inflammatory modulator. Keywords: IL-13Rα2; IL-13 signaling; IL-32θ; STAT3 activation; PKCδ 1. Introduction Interleukin (IL) IL-13 is produced largely in Th2 lymphocytes and is implicated in the pathogenesis of allergic disorders [1,2]. The biological activities of IL-13 are modulated through a receptor complex composed of the IL-4 receptor alpha (Rα) associated with the IL-13Rα1 chain [3]. IL-13 can utilize both IL-4Rα/JAK2/STAT3 and IL-13Rα1/TYK2/STAT1/STAT6 signaling pathways to regulate the expression of some critical inflammatory genes [4]. In addition, IL-13 receptor alpha subunit 2 (IL-13Rα2), a unique receptor of IL-13, has recently been reported to contribute to signaling, which is distinct from its original definition as a decoy receptor of IL-13 due to the lack of region for signal transduction [5]. A low level of IL-13Rα2 mRNA expression has been detected in promonocytic U937 cells and fibroblasts [3]. Int. J. Mol. Sci. 2019, 20, 1949; doi:10.3390/ijms20081949 www.mdpi.com/journal/ijms