Interleukin 23 regulates proliferation of lung cancer cells in a concentration-dependent way in association with the interleukin-23 receptor
Open Access
- 17 December 2012
- journal article
- research article
- Published by Oxford University Press (OUP) in Carcinogenesis: Integrative Cancer Research
- Vol. 34 (3), 658-666
- https://doi.org/10.1093/carcin/bgs384
Abstract
A proinflammatory cytokine, interleukin 23 (IL-23), plays a role in tumor progression by inducing inflammation in the tumor microenvironment, although there is debate about its role in carcinogenesis. Direct effects of IL-23 on tumor cells have been reported rarely, and contradictory effects have been observed. Here, we studied such effects of IL-23 in lung cancer cells in vitro and in vivo and explored the underlying mechanism. We found IL-23 receptor expression in tissues from lung adenocarcinoma and small cell carcinoma but not in lung squamous cell carcinoma tissue. Interestingly, different concentrations of IL-23 had opposite effects in the same types of cells. We confirmed that the different effects could be explained by differences in binding to the IL-23 receptor (subunits IL-23r and IL-12Rβ1). Low concentrations of IL-23 promoted the proliferation of IL-23 receptor-positive A549 and SPCA-1 lung cancer cells by binding to IL-23r, whereas high concentrations of IL-23 inhibited proliferation of these cells by binding to both IL-23r and IL-12Rβ1. In contrast, IL-23 had no effect on IL-23 receptor-negative SK-MES-1 cells. IL-23 regulated the growth of human lung cancer cells through its effects on STAT3 expression and phosphorylation in a concentration-dependent way; the Ki-67 gene was involved in these processes. Our findings demonstrate for the first time that IL-23 affects the proliferation of IL-23 receptor-positive lung cancer cells and that this effect is dependent on the IL-23 concentration. This can explain at least part of the inconsistent reports on the role of IL-23 in the progression of carcinogenesis.Keywords
This publication has 40 references indexed in Scilit:
- VEGF-Mediated STAT3 Activation Inhibits Retinal Vascularization by Down-Regulating Local Erythropoietin ExpressionThe American Journal of Pathology, 2012
- The protective role of TLR6 in a mouse model of asthma is mediated by IL-23 and IL-17AJCI Insight, 2011
- Genomic views of STAT function in CD4+ T helper cell differentiationNature Reviews Immunology, 2011
- Annexin A1 released from apoptotic cells acts through formyl peptide receptors to dampen inflammatory monocyte activation via JAK/STAT/SOCS signallingEMBO Molecular Medicine, 2011
- IL-23 suppresses innate immune response independently of IL-17A during carcinogenesis and metastasisProceedings of the National Academy of Sciences of the United States of America, 2010
- Expression of Interleukin-1 Receptor–Associated Kinase-1 in Non–Small Cell Lung Carcinoma and Preneoplastic LesionsClinical Cancer Research, 2010
- Cancer Statistics, 2008CA: A Cancer Journal for Clinicians, 2008
- Selective regulatory function of Socs3 in the formation of IL-17-secreting T cellsProceedings of the National Academy of Sciences of the United States of America, 2006
- IL-23 is essential for T cell–mediated colitis and promotes inflammation via IL-17 and IL-6JCI Insight, 2006
- Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brainNature, 2003