YAKHAK HOEJI (약학회지)

The Pharmaceutical Society of Korea (대한약학회)
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Effect of Corticosterone Pretreatment on the Production of LPS-Induced Inflammatory Mediators in Hepa1c1c-7 Cells

Hepa1c1c-7 Cell에서 리포폴리사카라이드로 유도된 염증성 매개인자 생산에 있어서 코르티코스테론 전처리 효과

  • 채병숙 (우석대학교 약학대학 약학과)
  • Received : 2015.10.05
  • Accepted : 2015.12.01
  • Published : 2016.02.29
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Abstract

Endotoxemia induces production of inflammatory mediators and acute phase proteins, leading to multiorgan injury and systemic inflammation. Hypothalamic-pituitary-adrenal (HPA) axis activation and glucocorticoids (GCs) release modify endotoxemia-induced inflammatory responses. In the present study, we investigated whether pre-exposure of GCs influences endotoxin-induced production of inflammatory mediators in hepatocytes. Hepa1c1c-7 cells were pretreated with low concentrations of corticosterone for 24 h and then cultured without corticosterone in the presence or absence of LPS. Our results demonstrated that LPS alone significantly enhanced production of IL-6 and CRP but reduced vascular endothelial growth factor (VEGF) compared to controls. Combination of corticosterone pretreatment and LPS significantly upregulated production of IL-6, IL-$1{\beta}$, and VEGF but downregulated CRP compared to those in LPS alone. These findings suggest that in low concentration of corticosterone-preexposed hepatocytes, endotoxemia may induce upregulation of IL-6, IL-$1{\beta}$, VEGF and but downregulation of CRP.

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References

  1. Johnson, H. L., Chiou, C. C. and Cho, C. T. : Applications of acute phase reactants in infectious diseases. J. Microbiol. Immunol. Infect. 32, 73 (1999).
  2. Morrison, D. C. and Ryan, J. L. : Bacterial endotoxins and host immune responses. Adv. Immunol. 28, 293 (1979).
  3. Wiernsperger, N. : Hepatic function and the cardiometabolic syndrome. Diabetes Metab. Syndr. Obes. 10, 379 (2013).
  4. Toth, C. A. and Thomas, P. : Liver endocytosis and Kupffer cells. Hepatology 16, 255 (1992).
  5. Saad, B., Frei, K., Schol, F. A., Fontana, A. and Maier, P. : Hepatocyte-derived interleukin-6 and tumor-necrosis factor alpha mediate the lipopolysaccharide-induced acute-phase response and nitric oxide release by cultured rat hepatocytes. Eur. J. Biochem. 229, 349 (1995). https://doi.org/10.1111/j.1432-1033.1995.0349k.x
  6. Beishuizen, A. and Thijs, L. G. : Endotoxin and the hypothalamo-pituitary-adrenal (HPA) axis. J. Endotoxin Res. 9, 3 (2003).
  7. Turnbull, A. V. and Rivier, C. L. : Regulation of the hypothalamicpituitary-adrenal axis by cytokines: actions and mechanisms of action. Physiol. Rev. 70, 1 (1999).
  8. Kasahara, E., Sekiyama, A., Hori, M., Kuratsune, D., Fujisawa, N., Chida, D., Hiramoto, K., Li, J., Okamura, H., Inoue, M. and Kitagawa, S. : Stress-induced glucocorticoid release upregulates uncoupling protein-2 expression and enhances resistance to endotoxin-induced lethality. Neuroimmunomodulation 22, 279 (2015). https://doi.org/10.1159/000368802
  9. Annane, D., Bellissant, E. and Bollaert, P. E. : Corticosteroids in the treatment of severe sepsis and septic shock in adults: a systematic review. JAMA 301, 2362 (2009). https://doi.org/10.1001/jama.2009.815
  10. Swain, M. G., Appleyard, C., Wallace, J., Wong, H. and Le, T. : Endogenous glucocorticoids released during acute toxic liver injury enhance hepatic IL-10 synthesis and release. Am. J. Physiol. Gastrointest. Liver Physiol. 276, G199 (1999). https://doi.org/10.1152/ajpgi.1999.276.1.G199
  11. Chida, Y., Sudo, N. and Kubo, C. : Does stress exacerbate liver diseases? J. Gastroenterol. Hepatol. 21(1 Pt 2), 202 (2006). https://doi.org/10.1111/j.1440-1746.2006.04110.x
  12. Shibli-Rahhal, A., Van Beek, M. and Schlechte, J. A. : Cushing's syndrome. Clin. Dermatol. 24, 260 (2006). https://doi.org/10.1016/j.clindermatol.2006.04.012
  13. Prowse, K. R. and Baumann, H. : Interleukin-1 and interleukin-6 stimulate acute-phase protein production in primary mouse hepatocytes. J. Leukoc. Biol. 45, 55 (1989). https://doi.org/10.1002/jlb.45.1.55
  14. Ganapathi, M. K., May, L. T., Schultz, D., Brabenec, A., Weinstein, J., Sehgal, P. B. and Kushner, I. : Role of interleukin- 6 in regulating synthesis of C-reactive protein and serum amyloid A in human hepatoma cell lines. Biochem. Biophys. Res. Commun. 157, 271 (1988). https://doi.org/10.1016/S0006-291X(88)80043-3
  15. Depraetere, S., Willems, J. and Joniau, M. : Stimulation of CRP secretion in HepG2 cells: cooperative effect of dexamethasone and interleukin 6. Agents Actions 34, 369 (1991). https://doi.org/10.1007/BF01988730
  16. Ganapathi, M. K., Rzewnicki, D., Samols, D., Jiang, S. L. and Kushner, I. : Effect of combinations of cytokines and hormones on synthesis of serum amyloid A and C-reactive protein in Hep 3B cells. J. Immunol. 147, 1261 (1991).
  17. Liao, J., Keiser, J. A., Scales, W. E., Kunkel, S. L. and Kluger, M. J. : Role of corticosterone in TNF and IL-6 production in isolated perfused rat liver. Am. J. Physiol. 268(3 Pt 2), R699 (1995).
  18. Meddings, J. B. and Swain, M. G. : Environmental stressinduced gastrointestinal permeability is mediated by endogenous glucocorticoids in the rat. Gastroenterology 119, 1019 (2000). https://doi.org/10.1053/gast.2000.18152
  19. Ramadori, G. and Armbrust, T. : Cytokines in the liver. Eur. J. Gastroenterol. Hepatol. 13, 777 (2001). https://doi.org/10.1097/00042737-200107000-00004
  20. Gong, X. W., Yang, Q. H., Yan, H. Z., Zhang, Y. P., Liang, Y. J., Liu, Y. Z., Zhang, J.-W., Lin, C. M., Jin, X., Zimmers, T. A., Perez, E. A., Pierce, R. H., Zhang, Z. and Koniaris, L. G. : Paradoxical effects of short- and long-term interleukin-6 exposure on liver injury and repair. Hepatology 43, 474 (2006). https://doi.org/10.1002/hep.21087
  21. Wustefeld, T., Rakemann, T., Kubicka, S., Manns, M. P. and Trautwein, C. : Hyperstimulation with interleukin 6 inhibits cell cycle progression after hepatectomy in mice. Hepatology 32, 514 (2000). https://doi.org/10.1053/jhep.2000.16604
  22. Li, X., Wang, Z., Zou, Y., Lu, E., Duan, J., Yang, H., Wu, Q., Zhao, X., Wang, Y., You, L., He, L., Xi, T. and Yang, Y. : Pretreatment with lipopolysaccharide attenuates diethylnitrosamine-caused liver injury in mice via TLR4-dependent induction of Kupffer cell M2 polarization. Immunol. Res. 62, 137 (2015). https://doi.org/10.1007/s12026-015-8644-2
  23. Geisterfer, M., Richards, C., Baumann, M., Fey, G., Gywnne, D. and Gauldie, J. : Regulation of IL-6 and the hepatic IL-6 receptor in acute inflammation in vivo. Cytokine 5, 1 (1993). https://doi.org/10.1016/1043-4666(93)90017-Y
  24. Zhou, D., Kusnecov, A. W., Shurin, M. R., DePaoli, M. and Rabin, B. S. : Exposure to physical and psychological stressors elevates plasma interleukin 6: relationship to the activation of hypothalamic-pituitary-adrenal axis. Endocrinology 133, 2523 (1993). https://doi.org/10.1210/endo.133.6.8243274
  25. Kitamura, H., Konno, A., Morimatsu, M., Jung, B. D., Kimura, K. and Saito, M. : Immobilization stress increases hepatic IL-6 expression in mice. Biochem. Biophys. Res. Commun. 238, 707 (1997). https://doi.org/10.1006/bbrc.1997.7368
  26. Quan, N., Avitsur, R., Stark, J. L., He, L., Shah, M., Caligiuri, M., Padgett, D. A., Marucha, P. T. and Sheridan, J. F. : Social stress increases the susceptibility to endotoxic shock. J. Neuroimmunol. 115, 36 (2001). https://doi.org/10.1016/S0165-5728(01)00273-9
  27. Panesar, N., Tolman, K. and Mazuski, J. E. : Endotoxin stimulates hepatocyte interleukin-6 production. J. Surg. Res. 85, 251 (1999). https://doi.org/10.1006/jsre.1999.5648
  28. Shimizu, H., Miyazaki, M., Wakabayashi, Y., Mitsuhashi, N., Kato, A., Ito, H., Nakagawa, K., Yoshidome, H., Kataoka, M. and Nakajima, N. : Vascular endothelial growth factor secreted by replicating hepatocytes induces sinusoidal endothelial cell proliferation during regeneration after partial hepatectomy in rats. J. Hepatol. 34, 683 (2001). https://doi.org/10.1016/S0168-8278(00)00055-6
  29. Walter, T. J., Cast, A. E., Huppert, K. A. and Huppert, S. S. : Epithelial VEGF signaling is required in the mouse liver for proper sinusoid endothelial cell identity and hepatocyte zonation in vivo. Am. J. Physiol. Gastrointest. Liver Physiol. 306, G849 (2014). https://doi.org/10.1152/ajpgi.00426.2013
  30. Gao, T., Lin, Z. and Jin, X. : Hydrocortisone suppression of the expression of VEGF may relate to toll-like receptor (TLR) 2 and 4. Curr. Eye Res. 34, 777 (2009). https://doi.org/10.1080/02713680903067919
  31. Carvalho, L. A., Torre, J. P., Papadopoulos, A. S., Poon, L., Juruena, M. F., Markopoulou, K., Cleare, A. J. and Pariante, C. M. : Lack of clinical therapeutic benefit of antidepressants is associated overall activation of the inflammatory system. J. Affect Disord. 148, 136 (2013). https://doi.org/10.1016/j.jad.2012.10.036
  32. Zong, L., Yu, Q. H., Du, Y. X. and Deng, X. M. : Edaravone protects endotoxin-induced liver injury by inhibiting apoptosis and reducing proinflammatory cytokines. Braz. J. Med. Biol. Res. 47, 231 (2014). https://doi.org/10.1590/1414-431X20133186
  33. Kramer, F., Torzewski, J., Kamenz, J., Veit, K., Hombach, V., Dedio, J. and Ivashchenko, Y. : Interleukin-1beta stimulates acute phase response and C-reactive protein synthesis by inducing an NFkappaB- and C/EBPbeta-dependent autocrine interleukin-6 loop. Mol. Immunol. 45, 2678 (2008). https://doi.org/10.1016/j.molimm.2007.12.017
  34. Weinhold, B. and Ruther, U. : Interleukin-6-dependent and - independent regulation of the human C-reactive protein gene. Biochem. J. 327, 425 (1997). https://doi.org/10.1042/bj3270425
  35. Woods, C. P., Hazlehurst, J. M. and Tomlinson, J. W. : Glucocorticoids and non-alcoholic fatty liver disease. J. Steroid. Biochem. Mol. Biol. 154, 94 (2015). https://doi.org/10.1016/j.jsbmb.2015.07.020
  36. Hribal, M. L., Fiorentino, T. V. and Sesti, G. : Role of C Reactive Protein (CRP) in leptin resistance. Curr. Pharm. 20, 609 (2014). https://doi.org/10.2174/13816128113199990016
  37. Dupuy, A. M., Terrier, N., Senecal, L., Morena, M., Leray, H., Canaud, B. and Cristol, J. P. : Is C-reactive protein a marker of inflammation? Nephrologie 24, 337 (2003).
  38. Xu, W., Chen, B., Guo, L., Li, Z., Zhao, Y. and Zeng, H. : Highsensitivity CRP: possible link between job stress and atherosclerosis. Am. J. Ind. Med. 58, 773 (2015). https://doi.org/10.1002/ajim.22470
  39. Lu, Z. Q., Lu, J. X. and Deng, Y. J. : Glucocorticoids offer protection against myocardial injury in a murine model of sepsis. Int. J. Clin. Exp. Med. 8, 12211 (2015).