Molecular & Cellular Toxicology

The Korean Society of Toxicogenomics and Toxicoproteomics (대한독성유전 단백체학회)
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Paw Edema was Reduced in Carrageenan Induced Acute Inflammation in Stat4 Deficient Mice

  • Zheng, Long-Tai (Department of Pharmacology, Kohwang Medical Research Institute, College of Medicine, Kyung Hee University) ;
  • Baik, Haing-Woon (Department of Biochemistry and Molecular Biology, School of Medicine, Eulji University) ;
  • Lee, Seong-Kyu (Department of Biochemistry and Molecular Biology, School of Medicine, Eulji University) ;
  • Cho, Jeong-Je (Department of Microbiology, College of Medicine, Kyung Hee University) ;
  • Park, Cheung-Seog (Department of Microbiology, College of Medicine, Kyung Hee University) ;
  • Hong, Mee-Suk (Department of Pharmacology, Kohwang Medical Research Institute, College of Medicine, Kyung Hee University) ;
  • Chung, Joo-Ho (Department of Pharmacology, Kohwang Medical Research Institute, College of Medicine, Kyung Hee University) ;
  • Yim, Sung-Vin (Department of Pharmacology, Kohwang Medical Research Institute, College of Medicine, Kyung Hee University)
  • Published : 2006.12.31
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Abstract

Signal transducer and activator of transcription 4 (STAT4) is one of the important mediators in generating inflammation and immune responses. To address the role of Stat4 in carrageenan induced acute inflammation, we performed paw edema measurement and 7.4 k mouse cDNA microarray analysis in carrageenan induced acute inflammation in Stat4 knockout (-/-) mice. Male BALB/c (n=8) and Stat4 -/- (n=5) were used and paw edema was induced with injection of $30\;{\mu}L$ of 1% carrageenan into plantar surface of right hind paw. Next, we isolated the mRNA in mouse whole brain and analyzed cDNA microarray profiles for the changes of the brain expression in Stat4 -/- mice. Interestingly, the increase in paw volume of Stat4 -/- mice was reduced by about 30% as compared to that of wild type. The cDNA microarray analysis revealed the altered expressions of several cytokines (Tnf, Il6, and Il4) and pain-associated proteins (Ptgs2, Gabra6, and Gabbr1) in Stat4 -/- mice. Our results suggest that Stat4 may be related to the inhibitory responses on carrageenan induced acute inflammation.

Keywords

References

  1. Morinobu, A. et al. STAT4 serine phosphorylation is critical for IL-12-induced IFN-gamma production but not for cell proliferation. Proc. Natl. Acad. Sci. U.S.A. 99, 2281-12286 (2002)
  2. Kaplan, M.H., Sun, Y., Hoe, T.Y. & Grusby, M.J. Impaired IL-12 responses and enhanced development of Th2 cells in Stat4-deficient mice. Nature 382, 174- 177 (1996) https://doi.org/10.1038/382174a0
  3. Gollob, J.A. et al. Phase I trial of twice-weekly intravenous interleukin 12 in patients with metastatic renal cell cancer or malignant melanoma: ability to maintain IFN-gamma induction is associated with clinical response. Clin. Cancer Res. 6, 1678-1692 (2000)
  4. Svensson, C.I. et al. Spinal phospholipase A2 in inflammatory hyperalgesia: role of the small, secretary phospholipase A2. Neuroscience 133, 543-553 (2005) https://doi.org/10.1016/j.neuroscience.2005.01.024
  5. Abe, T. et al. Liver injury due to sequential activation of natural killer cells and natural killer T cells by carrageenan. J. Hepatol. 36, 614-623 (2002) https://doi.org/10.1016/S0168-8278(02)00022-3
  6. Cabot, P.J., Carter, L., Schafer, M. & Stein, C. Immune cell-derived beta-endorphin. Production, release, and control of inflammatory pain in rats. J. Clin. Invest. 100, 142-148 (1997) https://doi.org/10.1172/JCI119506
  7. Ferreira, S.H., Lorenzetti, B.B., Bristow, A.F. & Poole, S. Interleukin-1 beta as a potent hyperalgesic agent antagonized by a tripeptide analogue. Nature 334, 698-700 (1988) https://doi.org/10.1038/334698a0
  8. Cunha, F.Q., Poole, S., Lorenzetti, B.B. & Ferreira, S.H. The pivotal role of tumour necrosis factor alpha in the development of inflammatory hyperalgesia. Br. J. Pharmacol. 107, 660-664 (1992) https://doi.org/10.1111/j.1476-5381.1992.tb14503.x
  9. Gold, M.S. Tetrodotoxin-resistant Na+currents and inflammatory hyperalgesia. Proc. Natl. Acad. Sci. U.S.A. 96, 7645-7649 (1999)
  10. Cunha, F.Q. et al. Cytokine-mediated inflammatory hyperalgesia limited by interleukin-4. Br. J. Pharmacol. 126, 45-50 (1999) https://doi.org/10.1038/sj.bjp.0702266
  11. Poole, S. et al. Cytokine-mediated inflammatory hyperalgesia limited by interleukin-10. Br. J. Pharmacol. 115, 684-688 (1995) https://doi.org/10.1111/j.1476-5381.1995.tb14987.x
  12. Lorenzetti, B.B. et al. Cytokine-mediated inflammatory hyperalgesia limited by interleukin-13. Eur. Cytokine Netw. 12, 260-267 (2001)
  13. Cunha, J.M., Cunha, F.Q., Poole, S. & Ferreira, S.H. Cytokine-mediated inflammatory hyperalgesia limited by interleukin-1 receptor antagonist. Br. J. Pharmacol.130, 1418-1424 (2000) https://doi.org/10.1038/sj.bjp.0703434
  14. Gamache, D.A., Povlishock, J.T. & Ellis, E.F. Effect of dexamethasone, indomethacin, ibuprofen, and probenecid on carrageenan-induced brain inflammation. J. Neurosurg. 65, 679-685 (1986) https://doi.org/10.3171/jns.1986.65.5.0679
  15. Lenzi, R. et al. Phase I study of intraperitoneal recombinant human interleukin 12 in patients with Mullerian carcinoma, astrointestinal primary malignancies and mesothelioma. Clin. Cancer Res. 8, 3686-3695 (2002)
  16. Weiss, G.R. et al. Phase 1 study of the intravesical administration of recombinant human interleukin-12 in patients with recurrent superficial transitional cell carcinoma of the bladder. J. Immunother. 26, 343-348 (2003) https://doi.org/10.1097/00002371-200307000-00006
  17. Kang, W.K. et al. Interleukin 12 gene therapy of cancer by peritumoral injection of transduced autologous fibroblasts: outcome of a phase I study. Hum. Gene Ther. 12, 671-684 (2001) https://doi.org/10.1089/104303401300057388
  18. Cunha, F.Q. et al. Cytokine-mediated inflammatory hyperalgesia limited by interleukin-4. Br. J. Pharmacol. 126, 45-50 (1999) https://doi.org/10.1038/sj.bjp.0702266