Role of Oxygen Free Radical in the Expression of Interleukin-8 and Interleukin-$1{\beta}$ Gene in Mononuclear Phagocytic Cells

내독소에 의한 말초혈액 단핵구의 IL-8 및 IL-$1{\beta}$ 유전자 발현에서 산소기 역할에 관한 연구

  • Kang, Min-Jong (Department of Internal Medicine and Tuberculosis Research Institute, Seoul National University College of Medicine) ;
  • Kim, Jae-Yeol (Department of Internal Medicine and Tuberculosis Research Institute, Seoul National University College of Medicine) ;
  • Park, Jae-Seok (Department of Internal Medicine and Tuberculosis Research Institute, Seoul National University College of Medicine) ;
  • Lee, Seung-Joon (Department of Internal Medicine and Tuberculosis Research Institute, Seoul National University College of Medicine) ;
  • Yoo, Chul-Gyu (Department of Internal Medicine and Tuberculosis Research Institute, Seoul National University College of Medicine) ;
  • Kim, Young-Whan (Department of Internal Medicine and Tuberculosis Research Institute, Seoul National University College of Medicine) ;
  • Han, Sung-Koo (Department of Internal Medicine and Tuberculosis Research Institute, Seoul National University College of Medicine) ;
  • Shim, Young-Soo (Department of Internal Medicine and Tuberculosis Research Institute, Seoul National University College of Medicine)
  • 강민종 (서울대학교 의과대학 내과학교실 및 결핵 연구소) ;
  • 김재열 (서울대학교 의과대학 내과학교실 및 결핵 연구소) ;
  • 박재석 (서울대학교 의과대학 내과학교실 및 결핵 연구소) ;
  • 이승준 (서울대학교 의과대학 내과학교실 및 결핵 연구소) ;
  • 유철규 (서울대학교 의과대학 내과학교실 및 결핵 연구소) ;
  • 김영환 (서울대학교 의과대학 내과학교실 및 결핵 연구소) ;
  • 한성구 (서울대학교 의과대학 내과학교실 및 결핵 연구소) ;
  • 심영수 (서울대학교 의과대학 내과학교실 및 결핵 연구소)
  • Published : 1995.12.31

Abstract

Background: Oxygen free radicals have generally been considered as cytotoxic agents. On the other hand, recent results suggest that small nontoxic amounts of these radicals may act a role in intracellular signal transduction pathway and many efforts to reveal the role of these radicals as secondary messengers have been made. It is evident that the oxygen radicals are released by various cell types in response to extracellular stimuli including LPS, TNF, IL-1 and phorbol esters, all of which translocate the transcription factor $NF{\kappa}B$ from cytoplasm to nucleus by releasing an inhibitory protein subunit, $I{\kappa}B$. Activation of $NF{\kappa}B$ is mimicked by exposure to mild oxidant stress, and inhibited by agents that remove oxygen radicals. It means the cytoplasmic form of the inducible tanscription factor $NF{\kappa}B$ might provide a physiologically important target for oxygen radicals. At the same time, it is well known that LPS induces the release of oxygen radicals in neutrophil with the activation of $NF{\kappa}B$. From above facts, we can assume the expression of IL-8 and IL-$1{\beta}$ gene by LPS stimulation may occur through the activation of $NF{\kappa}B$, which is mediated through the release of $I{\kappa}B$ by increasing amounts of oxygen radicals. But definitive evidence is lacking about the role of oxygen free radicals in the expression of IL-8 and IL-$1{\beta}$ gene in mononuclear phagocytic cells. We conducted a study to determine whether oxygen radicals act a role in the expression of IL-8 and IL-$1{\beta}$ gene in mononuclear phagocytic cells. Method: Human peripheral blood monocytes were isolated from healthy volunteers. Time and dose relationship of $H_2O_2$-induced IL-8 and IL-$1{\beta}$ mRNA expression was observed by Northern blot analysis. To evaluate the role of oxygen radicals in the expression of IL-8 and IL-$1{\beta}$ mRNA by LPS stimulation, pretreatment of various antioxiants including PDTC, TMTU, NAC, ME, Desferrioxamine were done and Northern blot analysis for IL-8 and IL-$1{\beta}$ mRNA was performed. Results: In PBMC, dose and time dependent expression of IL-8 and IL-$1{\beta}$ mRNA by exogenous $H_2O_2$ was not observed. But various antioxidants suppressed the expression of LPS-induced IL-8 and IL-$1{\beta}$ mRNA expression of PBMC and the suppressive activity was most prominant when the pretreatment was done with TMTU. Conclusion: Oxygen free radical may have some role in the expression of IL-8 and IL-$1{\beta}$ mRNA of PBMC but that radical might not be $H_2O_2$.

Acknowledgement

Supported by : 서울대학교병원