A proinflammatory cytokine interleukin‐32β promotes the production of an anti‐inflammatory cytokine interleukin‐10

Abstract

A new proinflammatory cytokine interleukin-32 (IL-32) has six isoforms. Although IL-32 can be detected in sera from patients suffering from Crohn's disease and rheumatoid arthritis, it is unclear which isoforms are involved. To this end, we investigated the functions of the most abundant IL-32b by generating K562-IL-32b stable cell lines. This report confirms, using IL-32 small interfering RNA, that IL-32b induces an anti-inflammatory cytokine IL-10 in K562-IL-32b cells and U937 promonocytic cells, which express endogenous IL-32b upon phorbol 12-myristate 13-acetate (PMA) treatment, and monocyte-derived dendritic cells (DC) upon lipopolysaccharide (LPS) treatment. Interleukin-32b was induced in monocyte-derived macrophages by LPS and in monocyte-derived DC by LPS, poly(I:C), or anti-CD40 antibody, but was not induced by PMA. We showed that IL-32b expression was increased in a time-dependent manner in monocyte-derived DC upon LPS treatment and peaked at 24 hr. Production of IL-10 was exactly coincident with IL-32b expression, but IL-1b and tumour necrosis factor-a production peaked at 6 hr after LPS treatment, then steeply declined. Interleukin-12 p40 was induced at 9 hr and gradually increased until 48 hr, at which time IL-32b and IL-10 were no longer increased. Knock-down of IL-32b by IL-32 small interfering RNA led to the decrease of IL-10, but the increase of IL-12 in monocytederived DC, which means that IL-32b promotes IL-10 production, but limits IL-12 production. We also showed that IL-10 neutralization increases IL-12, IL-1b and tumour necrosis factor-a production, which implies that IL-10 suppresses such proinflammatory cytokines. Taken together, our results suggest that IL-32b upregulates the production of an anti-inflammatory cytokine IL-10, and then IL-10 suppresses proinflammatory cytokines.Keywords: cytokine; dendritic cell; inflammation; interleukin-10; interleukin-32Please cite this article in press as: Kang J.-W. et al. A proinflammatory cytokine interleukin-32b promotes the production of an anti-inflammatory cytokine interleukin-10, Immunology (2009)

Interleukin (IL)-32β-mediated CCAAT/Enhancer-binding Protein α (C/EBPα) Phosphorylation by Protein Kinase Cδ (PKCδ) Abrogates the Inhibitory Effect of C/EBPα on IL-10 Production

“…We previously reported that IL-32␤ promotes IL-10 production in myeloid cells (28). In this study, we further verified our results and demonstrated an intracellular mediatory role of IL-32␤ for IL-10 production by showing that IL-32␤ promoted IL-10 production in a PKC␦-dependent way, where it mediated the phosphorylation of C/EBP␣ Ser-21 by PKC␦.…”

“…Stimulation-We demonstrated previously that IL-32␤ promoted the production of the anti-inflammatory cytokine IL-10 in myeloid cells (28). To verify that IL-32␤ is involved in IL-10 production, we knocked down IL-32␤ by using siRNA in U937 cells (Fig.…”

Paradoxical effects of constitutive human IL-32γ in transgenic mice during experimental colitis

“…In support of this concept, monocytes from human PBMC were differentiated into dendritic cells (DC) and stimulated with lypopolysaccharides (LPS). Gene expression of IL-32β paralleled the secretion of IL-10 reaching levels of 5-6 ng/mL between 24 and 48 h (18). Silencing of endogenous IL-32 in LPS-stimulated DC cells resulted in a 50% decrease in IL-10 production compared with scrambled siRNA (18).…”

“…IL-32β is also active (18,19). The presence of IL-32 protein has been reported in synovial tissues of rheumatoid arthritis (9,20,21) and Mycobacterium tuberculosis infections (22,23).…”

Evaluation of IL-32 levels in gingival tissue and serum of experimental periodontitis model

“…Reportedly, IL-32β upregulated the IL-10 generation by interfering with the discharge/action of protein kinase C in myeloid cells and that IL-32δ lessened the generation of this cytokine in a dosage expanding way in U937 cells (36). However, there are 6 subtypes of IL-32, and until now their part in periodontitis is undefined.…”