Hibiscus syriacus Leaves Upregulate p62/SQSTM1 through TLR4/p38, JNK, and NF-κB/Nrf2 Signaling Pathway in RAW264.7 Cells
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
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, HSL increased p62/SQSTM1 expression. Inhibition of TLR4, p38, JNK, and NF-κB blocked HSL-mediated increase of p62/SQSTM1. HSL activated p38, JNK, and NF-κB signaling, but HSL-mediated activation of p38, JNK, and NF-κB signaling was reversed by TLR4 inhibition. In addition, HSL increased Nrf2 expression, but HSLmediated Nrf2 expression did not occur in the inhibition of TLR4, p38, JNK, and NF-κB. Taken together, it is believed that HSL-mediated autophagy may be dependent on activating Nrf2 expression via TLR4-dependent activation of p38, JNK, and NF-κB in macrophages.
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, HSL increased p62/SQSTM1 expression. Inhibition of TLR4, p38, JNK, and NF-κB blocked HSL-mediated increase of p62/SQSTM1. HSL activated p38, JNK, and NF-κB signaling, but HSL-mediated activation of p38, JNK, and NF-κB signaling was reversed by TLR4 inhibition. In addition, HSL increased Nrf2 expression, but HSLmediated Nrf2 expression did not occur in the inhibition of TLR4, p38, JNK, and NF-κB. Taken together, it is believed that HSL-mediated autophagy may be dependent on activating Nrf2 expression via TLR4-dependent activation of p38, JNK, and NF-κB in macrophages.
참고문헌 (23)
- Barker, R. N., "Antigen presentation by macrophages is enhanced by the uptake of necrotic, but not apoptotic, cells", Clin. Exp. Immunol, 127(2), pp.220~225 (2002)
- Chou, Y. J., "Vaccine adjuvant activity of a TLR4-activating synthetic glycolipid by promoting autophagy", Sci. Rep, 10, pp.8422~ (2020)
- Coffman, R. L., "Vaccine adjuvants : putting innate immunity to work", Immunity, 33, pp.492~503 (2010)
- Duque, G. A., "Macrophage cytokines : involvement in immunity and infectious diseases", Front. Immunol, 5, pp.491~ (2014)
- Fujita, K. I., "TLR4-mediated autophagy in macrophages is a p62-dependent type of selective autophagy of aggresome-like induced structures(ALIS)", Autophagy, 7(5), pp.552~554 (2011)
- Fujita, K. I., "Nrf2-mediated induction of p62 controls Toll-like receptor-4-driven aggresome-like induced structure formation and autophagic degradation", PNASU, 108(4), pp.1427~1432 (2011)
- 금나경, "Immunostimulatory Activity of Hibiscus syriacus L. Leaves in Mouse Macrophages, RAW264.7 cells, and Immunosuppressed Mice", 한국자원식물학회지, 35(6), pp.697~703 (2022), 한국자원식물학회
- Hirayama, D., "The phagocytic function of macrophage-enforcing innate immunity and tissue homeostasis", Int. J. Mol. Sci, 19(1), pp.92~ (2018)
- Karunarathne, W. A. H. M., "Anthocyanins from Hibiscus syriacus L. inhibit melanogenesis by activating the ERK signaling pathway", Biomolecules, 9(11), pp.645~ (2019)
- Kim Jae Hwan, "Immunomodulatory functional foods and their molecular mechanisms", Experimental and Molecular Medicine, 54, pp.1~11 (2022), 생화학분자생물학회[DOI]
- Komatsu, M., "Physiological significance of selective degradation of p62 by autophagy", FEBS Lett, 584, pp.1374~1378 (2010)
- Lamark, T., "NBR1 and p62 as cargo receptors for selective autophagy of ubiquitinated targets", Cell Cycle, 8, pp.1986~1990 (2009)
- Liu, T., "NF-κB signaling in inflammation. Signal Transduct", Target Ther, 2, pp.17023~ (2017)
- Puissant, A., "When autophagy meets cancer through p62", SQSTM1, 2012, pp.2, 397~413
- Schenten, D., "The control of adaptive immune responses by the innate immune system", Adv. Immunol, 109, pp.87~124 (2011)
- Steinhagen, F., "TLR-based immune adjuvants", Vaccine, 29, pp.3341~3355 (2011)
- Thimmulappa, R. K., "Nrf2 is a critical regulator of the innate immune response and survival during experimental sepsis", J. Clin. Invest, 116(4), pp.984~995 (2006)
- Toussi, D. N., "Immune adjuvant effect of molecularly-defined toll-like receptor ligands", Vaccines(Basel), 2, pp.323~353 (2014)
- van der Varrt, M., "The DNA damage-regulated autophagy modulator DRAM1 links mycobacterial recognition via TLRMYD88 to autophagic defense", Cell Host Microbe, 15(6), pp.753~767 (2014)
- Wu, M. Y., "Autophagy and macrophage functions : Inflammatory response and phagocytosis", Cells, 9(1), pp.70~ (2020)
- Xu, Y., "Toll-like receptor 4 is a sensor for autophagy associated with innate immunity", Immunity, 27(1), pp.135~144 (2007)
- Yazid, M. D., "Perturbation of PI3K", Akt signaling affected autophagy modulation in dystrophindeficient myoblasts, 2021, pp.19(1), 105~
- Zheng, Y. T., "The adaptor protein p62", SQSTM1 targets invading bacteria to the autophagy pathway, 2009, pp.183(9), 5909~5916
