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2023 Vol.36, Issue 4 Preview Page
Induction of Autophagy by Paeonia lactiflora Root Extracts through Upregulation p62/SQSTM1 in RAW264.7 Cells

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

Jin Boo Jeong1*
정 진부1*
1Professor, Department of Forest Science, Andong National University, Andong 36729, Korea
1국립안동대학교 산림과학과, 교수
*Corresponding Author
1 August 2023. pp. 275-281
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Abstract

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.

Keywords
Autophagy
Macrophage
Paeonia lactiflora
References
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. 10.1038/s41598-020-65422-132439945PMC7242473
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. 10.1111/j.1600-065X.2008.00725.x19120485PMC2788953
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. 10.4161/auto.7.5.1510121412052PMC3127216
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. 10.1073/pnas.101415610821220332PMC3029726
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. 10.3389/fphar.2011.00010
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. 10.1038/s41467-019-09598-930952952PMC6451001
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. 10.1016/j.cellsig.2012.01.02022333395
10
Johansen, T. and T. Lamark. 2011. Selective autophagy mediated by autophagic adapter proteins. Autophagy 7(3):279-296. 10.4161/auto.7.3.1448721189453PMC3060413
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. 10.1016/j.tiv.2009.06.01919540912
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. 10.1038/nrmicro86515031729PMC7097095
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. 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. 10.1007/978-1-60761-585-9_920099125
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. 10.1016/j.vaccine.2004.01.06115297065
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. 10.1172/JCI2579016585964PMC1421348
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. 10.1016/j.arabjc.2022.104132
19
Wu, M.Y. and J.H. Lu. 2020. Autophagy and macrophage functions: Inflammatory response and phagocytosis. Cells 9(1):70. 10.3390/cells901007031892110PMC7016593
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. 10.1046/j.1440-1711.1998.00748.x9682967
21
Zhang, L. and W. Wei. 2020. Anti-inflammatory and immunoregulatory effects of paeoniflorin and total glucosides of paeony. Pharmacol. Ther. 207:107452. 10.1016/j.pharmthera.2019.10745231836457
Information
  • Publisher :The Plant Resources Society of Korea
  • Publisher(Ko) :한국자원식물학회
  • Journal Title :Korean Journal of Plant Resources
  • Journal Title(Ko) :한국자원식물학회지
  • Volume : 36
  • No :4
  • Pages :275-281
  • Received Date : 2023-03-30
  • Revised Date : 2023-04-24
  • Accepted Date : 2023-04-24
  • DOI :https://doi.org/10.7732/kjpr.2023.36.4.275
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