Interleukin-4 up-regulates 15-hydroxyprostaglandin dehydrogenase (15-PGDH) in human lung cancer cells

Experimental Cell Research
Xiuling Chi, Hsin-Hsiung Tai

Abstract

IL-4, an anti-inflammatory cytokine, was found to stimulate 15-PGDH activity in A549 and other lung cancer cells. Increase in 15-PGDH activity was due to increased transcription and decreased protein turnover of 15-PGDH. MMP-9 was shown to result in decreased levels of 15-PGDH in A549 cells. IL-4 induced down-regulation of MMP-9 mRNA and up-regulation of TIMP-1, an inhibitor of MMP-9. These data suggest that IL-4-induced down-regulation of MMP-9 activity may contribute to up-regulation of 15-PGDH in A549 cells. The role of JAK-STAT6 in IL-4-induced 15-PGDH expression was examined by using inhibitors. Inhibitors of JAKs, kaempferol and JAK inhibitor I, attenuated IL-4-stimulated STAT6 phosphorylation and 15-PGDH activity in a comparable concentration-dependent manner. Furthermore, JAK inhibitor I blocked IL-4-induced down-regulation of MMP-9 mRNA and up-regulation of TIMP-1 but not IL-4-stimulated up-regulation of 15-PGDH mRNA. These results indicate that JAK-STAT6 participated in IL-4-induced up-regulation of 15-PGDH through inhibition of MMP-9-mediated degradation. The roles of other signaling kinases in IL-4-induced 15-PGDH expression were also examined by using various inhibitors. Inhibitors of various MAPKs, PI-3K and PKC a...Continue Reading

References

Aug 15, 1996·The Biochemical Journal·R BrinckmannJ R Habenicht
Jun 8, 1999·Annual Review of Immunology·K NelmsW E Paul
Jun 23, 1999·Proceedings of the National Academy of Sciences of the United States of America·P J JakobssonB Samuelsson
Aug 31, 2000·Annual Review of Biochemistry·W L SmithR M Garavito
Sep 28, 2000·Biochemical and Biophysical Research Communications·M Tong, H H Tai
May 16, 2001·Prostaglandins & Other Lipid Mediators·M FrenkianA Jullienne
Aug 6, 2002·Cytokine·Abigail E HuntBrian M J Foxwell
Nov 16, 2002·Prostaglandins & Other Lipid Mediators·Hsin-Hsiung TaiFengxiang Yan
Feb 1, 2003·Trends in Pharmacological Sciences·Kotha Subbaramaiah, Andrew J Dannenberg
Nov 16, 2004·The Journal of Biological Chemistry·Michael G BacklundRaymond N DuBois
Dec 3, 2004·Proceedings of the National Academy of Sciences of the United States of America·Min YanSanford D Markowitz
Feb 25, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Stephen CanfieldPaul Rothman
May 21, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Axel LorentzStephan C Bischoff
Oct 1, 2005·American Journal of Physiology. Gastrointestinal and Liver Physiology·Taisuke OtaniAndrew J Dannenberg
Apr 1, 2006·Biochemical and Biophysical Research Communications·Xiaoyan CuiSteven M Dubinett
Aug 4, 2006·Cancer Research·Ido WolfH Phillip Koeffler
Oct 10, 2006·Vitamins and Hormones·S Jaharul Haque, Pankaj Sharma
Mar 6, 2007·Experimental & Molecular Medicine·YoungHyun ShinJae-Hong Kim
Apr 10, 2007·The Journal of Allergy and Clinical Immunology·Xiuxia ZhouSally E Wenzel
Jul 10, 2007·Archives of Pharmacal Research·Chan Young ShinKwang Ho Ko
Sep 6, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jose R CortesJose Zamorano
Mar 14, 2008·Toxicology and Applied Pharmacology·Chih-Chung LinChuen-Mao Yang

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Citations

Mar 15, 2012·World Journal of Gastroenterology : WJG·Li-Hong LouKai Wu
Oct 25, 2011·Cancer Metastasis Reviews·Hsin-Hsiung Tai
Jul 19, 2011·Prostaglandins & Other Lipid Mediators·Hsin-Hsiung TaiMin Tong
Jul 15, 2011·Expert Opinion on Therapeutic Targets·William Cs ChoJoseph Sk Au
Aug 11, 2018·Cancer Metastasis Reviews·Dali TongJun Jiang

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