The Production Mechanism of TNF-${\alpha}$ and IL-6 by Group IIA Phospholipase $A_2$

IIA형 Phospholipase $A_2$에 의한 TNF-${\alpha}$와 IL-6 생성 기전

  • Ahn, Jae-Hong (Department of Obstetrics and Gynecology, College of Medicine, Yeungnam University) ;
  • Park, Dae-Won (Department of Biochemistry and Molecular Biology, College of Medicine, Yeungnam University) ;
  • Kim, Jin-Hee (Department of Obstetrics and Gynecology, College of Medicine, Yeungnam University) ;
  • Bae, Jei-Jun (Department of Obstetrics and Gynecology, College of Medicine, Yeungnam University) ;
  • Bae, Yeun-Kyoung (Department of Obstetrics and Gynecology, College of Medicine, Yeungnam University) ;
  • Park, Yoon-Ki (Department of Obstetrics and Gynecology, College of Medicine, Yeungnam University)
  • 안재홍 (영남대학교 의과대학 산부인과학교실) ;
  • 박대원 (영남대학교 의과대학 생화학.분자생물학교실) ;
  • 김진희 (영남대학교 의과대학 산부인과학교실) ;
  • 배제준 (영남대학교 의과대학 산부인과학교실) ;
  • 배연경 (영남대학교 의과대학 산부인과학교실) ;
  • 박윤기 (영남대학교 의과대학 산부인과학교실)
  • Published : 2004.12.30

Abstract

Background: Secretory phospholipase $A_2$ ($sPLA_2$) are a group of extracellular enzymes that release fatty acids at the sn-2 position of phospholipids. Group IIA $sPLA_2$ ($sPLA_2$-IIA) has been detected in the inflammatory fluids, and its plasma level increases in the inflammatory disease. This study examined the effect of $sPLA_2$-IIA on mouse macropahges in order to investigate the potential mechanism of $sPLA_2$-induced inflammation. Materials and Methods: Wild type $PLA_2$ and mutant H48Q $PLA_2$ were purified from HEK293 cells transfected with the corresponding plasmids, and the $PLA_2$ activities were measured using 1-palmitoyl-2-[1-$^{14}C$]linoleoyl-3-phosphatidylethanolamine as substrates. The TNF-${\alpha}$ and IL-6 released in the supernatants were determined by ELISA. In addition, the TNF-${\alpha}$ and IL-6 mRNA were analyzed by RT-PCR. Results: $sPLA_2$-IIA stimulated the production of TNF-${\alpha}$ and IL-6 in a dose- and time-dependent manner. In addition, the effect of $sPLA_2$-IIA on cytokine production from the macrophage was found to be associated with the accumulation of their specific mRNA. The mRNA levels of TNF-${\alpha}$ and IL-6 peaked at 2 and 6 hours in a time-dependent manner, respectively. Conclusion: In conclusion, the production of proinflammatory cytokine might be mediated by the binding of $sPLA_2$-IIA to the receptors.

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