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작약(Paeonia lactiflora) 뿌리 추출물의 대식세포에서 p62/SQSTM1 증가를 통한 자가포식 유도

Induction of Autophagy by Paeonia lactiflora Root Extracts through Upregulation p62/SQSTM1 in RAW264.7 Cells

  • 정진부 (국립안동대학교 산림과학과)
  • Jin Boo Jeong (Department of Forest Science, Andong National University)
  • 투고 : 2023.03.30
  • 심사 : 2023.04.24
  • 발행 : 2023.08.01

초록

본 연구에서 우리는 작약 뿌리 추출물이 TLR4/PI3K/Nrf2 신호전달을 통해 p62/SQSTM1을 증가시켜 대식세포에서 자가포식을 유도한다는 것을 확인하였다. 대식세포의 자가포식 유도는 선천성과 적응성 면역 반응 간의 연결을 강화해 백신 보조제 개발에 있어서 중요한 표적으로 사용되기 때문에, 작약 뿌리 추출물은 백신개발에 필수적인 백신보조제로의 활용이 가능할 것으로 생각된다.

Autophagy contributes to enhancing the immune system (innate and adaptive immune system) against foreign pathogens. Autophagy of macrophages is used as a major indicator for developing vaccine adjuvants to increase the adaptive immune response. In this study, PLR activated autophagy and increased p62/SQSTM1. The knockdown of p62/SQSTM1 attenuated PLR-mediated autophagy. Inhibition of TLR4 blocked PLR-mediated increase in p62/SQSTM1 level and autophagy induction. In addition, inhibition of PI3K blocked HSL-mediated increase of p62/SQSTM1. PLR increased Nrf2 level and the inhibition of TLR4 and PI3K reduced PLR-mediated increase of Nrf2. Taken together, it is believed that PLR may induce autophagy through upregulating p62/SQSTM1 via TLR4/PI3K/Nrf2 signaling pathway.

키워드

과제정보

본 논문은 농촌진흥청 연구사업(과제번호: PJ017090052022)의 지원에 의해 이루어진 것으로 이에 감사드립니다.

참고문헌

  1. Chen, G., L.X. Guo, X.H. Deng, Z.Y. Yin and J.J. Jing. 2008. Effects of total glucosides of paeony on nitric oxide and inducible nitric oxide synthase production in macrophages and its mechanism. Zhongguo Mian Yi Xue Za Zhi. 24:345-347.
  2. Chou, Y.J., C.C. Lin, I. Dzhagalov, N.J. Chen, C.H. Lin, C.C. Lin, S.T. Chen, K.H. Chen and S.L. Fu. 2020. Vaccine adjuvant activity of a TLR4-activating synthetic glycolipid by promoting autophagy. Sci. Rep. 10:8422.
  3. Delgado, M., S. Singh, S. de Haro, S. Master, M. Ponpuak, C. Dinkins, W. Ornatowski, I. Vergne and V. Deretic. 2009. Autophagy and pattern recognition receptors in innate immunity. Immunol. Rev. 227(1):189-202. https://doi.org/10.1111/j.1600-065X.2008.00725.x
  4. Fujita, K.I. and S.M. Srinivasula. 2011a. TLR4-mediated autophagy in macrophages is a p62-dependent type of selective autophagy of aggresome-like induced structures (ALIS). Autophagy 7(5):552-554. https://doi.org/10.4161/auto.7.5.15101
  5. Fujita, K.I., D.M. Maeda, Q. Xiao and S.M. Srinivasula. 2011b. Nrf2-mediated induction of p62 controls Toll-like receptor-4-driven aggresome-like induced structure formation and autophagic degradation. PNASU. 108(4):1427-1432. https://doi.org/10.1073/pnas.1014156108
  6. Geum, N.G., J.H. Yu, S.J. Park, M.Y. Choi, J.W. Lee, G.H. Park, H.Y. Kwon and J.B. Jeong. 2022. Immunostimulatory activity of Hibiscus syriacus L. leaves in mouse macrophages, RAW264.7 cells, and immunosuppressed mice. Korean J. Plant Res. 35(6):697-703.
  7. He, D.Y. and S.M. Dai. 2011. Anti-inflammatory and immunomodulatory effects of Paeonia lactiflora Pall., a traditional Chinese herbal medicine. Front. Pharmacol. 2:10.
  8. Iershov, A., I. Nemazanyy, C. Alkhoury, M. Girard, E. Barth, N. Cagnard, Al. Montagner, D. Chretien, E.I. Rugarli, H. Guillou, M. Pende and G. Panasyuk. 2019. The class 3 PI3K coordinates autophagy and mitochondrial lipid catabolism by controlling nuclear receptor PPARα. Nat. Commun. 10:1566.
  9. Into, T., M. Inomata, E. Takayama and T. Takigawa. 2012. Autophagy in regulation of Toll-like receptor signaling. Cell. Signal. 24(6):1150-1162. https://doi.org/10.1016/j.cellsig.2012.01.020
  10. Johansen, T. and T. Lamark. 2011. Selective autophagy mediated by autophagic adapter proteins. Autophagy 7(3):279-296. https://doi.org/10.4161/auto.7.3.14487
  11. Kim, I.D. and B.J. Ha. 2009. Paeoniflorin protects RAW 264.7 macrophages from LPS-induced cytotoxicity and genotoxicity. Toxicol. in Vitro 23:1014-1019. https://doi.org/10.1016/j.tiv.2009.06.019
  12. Kirkegaard, K., M.P. Taylor and W.T. Jackson. 2004. Cellular autophagy: Surrender, avoidance and subversion by micorganisms. Nat. Rev. Microbiol. 2:301-314. https://doi.org/10.1038/nrmicro865
  13. Lee, Y.J., M.S. Choi and P.S. Choi. 2022. Optimal conditions for adventitious root organogenesis from peony root explant callus cultures. J. Plant Biotechnol. 49:207-212. https://doi.org/10.5010/JPB.2022.49.3.207
  14. Li, J., M.Z. Chen and S.Y. Xu. 2007. Effect of total glucosides of paeony on prostaglandin E2 derived from peritoneal macrophages and related mechanisms in rats. Zhongguo Yao Li Xue Tong Bao. 10:267-270.
  15. Quesniaux, V., F. Erard and B. Ryffel. 2010. Adjuvant activity on murine and human macrophages. Methods Mol. Biol. 626:117-130. https://doi.org/10.1007/978-1-60761-585-9_9
  16. Rimaniol, A.C., G. Gras, F. Verdier, F. Capel, V.B. Grigoriev, F. Porcheray, E. Sauzeat, J.G. Fournier, P. Clayette, C.A. Siegrist and D. Dormont. 2004. Aluminum hydroxide adjuvant induces macrophage differentiation towards a specialized antigen-presenting cell type. Vaccine 22:3127-3135. https://doi.org/10.1016/j.vaccine.2004.01.061
  17. Thimmulappa, R.K., H. Lee, T. Rangasamy, S.P. Reddy, M. Yamamoto, T.W. Kensler and S. Biswal. 2006. Nrf2 is a critical regulator of the innate immune response and survival during experimental sepsis. J. Clin. Invest. 116(4):984-995. https://doi.org/10.1172/JCI25790
  18. Wang, X., N. Li, Y. Li, Y. Zhao, L. Zhang, Y. Sun, Y. Ohizumi, J. Xu and Y.A. Guo. 2022. novel polysaccharide from Paeonia lactiflora exerts anti-tumor activity via immunoregulation. Arab. J. Chem. 15(10):104132.
  19. Wu, M.Y. and J.H. Lu. 2020. Autophagy and macrophage functions: Inflammatory response and phagocytosis. Cells 9(1):70.
  20. Yamamoto, N. and V.R. Naraparaju. 1998. Structurally well-defined macrophage activating factor derived from vitamin D3-binding protein has a potent adjuvant activity for immunization. Immunol. Cell Biol. 76:237-244. https://doi.org/10.1046/j.1440-1711.1998.00748.x
  21. Zhang, L. and W. Wei. 2020. Anti-inflammatory and immunoregulatory effects of paeoniflorin and total glucosides of paeony. Pharmacol. Ther. 207:107452.