Effects of Herb-Partitioned Moxibustion on Autophagy and Immune Activity in the Colon Tissue of Rats with Crohn's Disease

Overview

Journal Evid Based Complement Alternat Med

Specialty Rehabilitation Medicine

Date 2022 Feb 7

PMID 35126598

Authors

Jimeng Zhao

Zhe Ma

Handan Zheng

Yan Huang

Luyi Wu

Huangan Wu

Yin Shi

Huirong Liu

Yanan Liu

Affiliations

Soon will be listed here.

Abstract

Objective: To investigate the mechanism of action of herb-partitioned moxibustion on CD from the perspective of autophagy and immunity.

Methods: The expression of microtubule-associated protein LC3II and SQSTM1/p62 in the colon tissues was detected by immunohistochemistry. Western blot was used to detect the expression of autophagic and immune-related proteins in the colon, such as LC3II, SQSTM1/p62, Beclin1, ATG16L1, NOD2, IRGM, IL-1, IL-17, and TNF-. mRNA levels of immune factors, such as IL-1, IL-17, and TNF-, and autophagy signaling molecules, such as PI3KC, AKT1, LKB1, and mTOR, were detected by RT-qPCR.

Results: Herb-partitioned moxibustion reduced the protein levels of ATG16L1, NOD2, IRGM, LC3II, and Beclin1 ( < 0.01) and both the protein and mRNA levels of IL-1, IL-17, and TNF- in CD rats ( < 0.01 or < 0.05), and it also increased the expression of SQSTM1/p62 protein ( < 0.01). The modulatory effects of herb-partitioned moxibustion on ATG16L1, NOD2, IRGM, LC3II, TNF-, and IL-17 protein and IL-1 protein and mRNA were better than those of mesalazine ( < 0.01 or < 0.05). Herb-partitioned moxibustion also reduced colon PI3KC, AKT1, and LKB1 mRNA expressions in CD rats ( < 0.01 or < 0.05) and increased mTOR protein expression ( < 0.05). And the modulatory effect of herb-partitioned moxibustion on AKT1 mRNA was better than that of mesalazine ( < 0.05).

Conclusion: Herb-partitioned moxibustion may inhibit excessively activated autophagy and modulate the expression of immune-related factors by regulating the LKB1-mTOR-PI3KC signal transduction networks, thereby alleviating intestinal inflammation in CD rats.

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References

He C, Klionsky D . Regulation mechanisms and signaling pathways of autophagy. Annu Rev Genet. 2009; 43:67-93. PMC: 2831538. DOI: 10.1146/annurev-genet-102808-114910. View

Jones E, Matthews Z, Gul L, Sudhakar P, Treveil A, Divekar D . Integrative analysis of Paneth cell proteomic and transcriptomic data from intestinal organoids reveals functional processes dependent on autophagy. Dis Model Mech. 2019; 12(3). PMC: 6451430. DOI: 10.1242/dmm.037069. View

Liao Y, Xu J, Qin B, Shi J, Qin C, Xie F . Advanced oxidation protein products impair autophagic flux in macrophage by inducing lysosomal dysfunction via activation of PI3K-Akt-mTOR pathway in Crohn's disease. Free Radic Biol Med. 2021; 172:33-47. DOI: 10.1016/j.freeradbiomed.2021.05.018. View

Lassen K, Xavier R . An alteration in ATG16L1 stability in Crohn disease. Autophagy. 2014; 10(10):1858-60. PMC: 4198368. DOI: 10.4161/auto.29963. View

Homer C, Richmond A, Rebert N, Achkar J, McDonald C . ATG16L1 and NOD2 interact in an autophagy-dependent antibacterial pathway implicated in Crohn's disease pathogenesis. Gastroenterology. 2010; 139(5):1630-41, 1641.e1-2. PMC: 2967588. DOI: 10.1053/j.gastro.2010.07.006. View

Kaplan G, Ng S . Understanding and Preventing the Global Increase of Inflammatory Bowel Disease. Gastroenterology. 2016; 152(2):313-321.e2. DOI: 10.1053/j.gastro.2016.10.020. View

Cooney R, Baker J, Brain O, Danis B, Pichulik T, Allan P . NOD2 stimulation induces autophagy in dendritic cells influencing bacterial handling and antigen presentation. Nat Med. 2009; 16(1):90-7. DOI: 10.1038/nm.2069. View

Iida T, Onodera K, Nakase H . Role of autophagy in the pathogenesis of inflammatory bowel disease. World J Gastroenterol. 2017; 23(11):1944-1953. PMC: 5360635. DOI: 10.3748/wjg.v23.i11.1944. View

Shpilka T, Weidberg H, Pietrokovski S, Elazar Z . Atg8: an autophagy-related ubiquitin-like protein family. Genome Biol. 2011; 12(7):226. PMC: 3218822. DOI: 10.1186/gb-2011-12-7-226. View

10.

Long S, He Y, Chen M, Cao K, Chen Y, Chen B . Activation of PI3K/Akt/mTOR signaling pathway triggered by PTEN downregulation in the pathogenesis of Crohn's disease. J Dig Dis. 2013; 14(12):662-9. DOI: 10.1111/1751-2980.12095. View

11.

Iida T, Yokoyama Y, Wagatsuma K, Hirayama D, Nakase H . Impact of Autophagy of Innate Immune Cells on Inflammatory Bowel Disease. Cells. 2018; 8(1). PMC: 6356773. DOI: 10.3390/cells8010007. View

12.

Jang Y, Kim J, Byun S . Modulation of Autophagy for Controlling Immunity. Cells. 2019; 8(2). PMC: 6406335. DOI: 10.3390/cells8020138. View

13.

Zhao J, Liu Y, Zheng H, Huang Y, Qi Q, Liu H . Effect of Herb-Partitioned Moxibustion on Autophagy and Immune-Associated Gene Expression Profiles in a Rat Model of Crohn's Disease. Evid Based Complement Alternat Med. 2019; 2019:3405146. PMC: 6431444. DOI: 10.1155/2019/3405146. View

14.

Yang L, Liu C, Zhao W, He C, Ding J, Dai R . Impaired Autophagy in Intestinal Epithelial Cells Alters Gut Microbiota and Host Immune Responses. Appl Environ Microbiol. 2018; 84(18). PMC: 6121970. DOI: 10.1128/AEM.00880-18. View

15.

Jeong Y, Kang M, Lee S, Kim C, Kim J, Kim T . Nod2 and Rip2 contribute to innate immune responses in mouse neutrophils. Immunology. 2014; 143(2):269-76. PMC: 4172142. DOI: 10.1111/imm.12307. View

16.

Rufini S, Ciccacci C, Di Fusco D, Ruffa A, Pallone F, Novelli G . Autophagy and inflammatory bowel disease: Association between variants of the autophagy-related IRGM gene and susceptibility to Crohn's disease. Dig Liver Dis. 2015; 47(9):744-50. DOI: 10.1016/j.dld.2015.05.012. View

17.

Mehto S, Jena K, Nath P, Chauhan S, Kolapalli S, Das S . The Crohn's Disease Risk Factor IRGM Limits NLRP3 Inflammasome Activation by Impeding Its Assembly and by Mediating Its Selective Autophagy. Mol Cell. 2019; 73(3):429-445.e7. PMC: 6372082. DOI: 10.1016/j.molcel.2018.11.018. View

18.

Netea-Maier R, Plantinga T, van de Veerdonk F, Smit J, Netea M . Modulation of inflammation by autophagy: Consequences for human disease. Autophagy. 2015; 12(2):245-60. PMC: 4836004. DOI: 10.1080/15548627.2015.1071759. View

19.

Germain M, Nguyen A, Le Grand J, Arbour N, Vanderluit J, Park D . MCL-1 is a stress sensor that regulates autophagy in a developmentally regulated manner. EMBO J. 2010; 30(2):395-407. PMC: 3025469. DOI: 10.1038/emboj.2010.327. View

20.

Steinbach E, Kobayashi T, Russo S, Sheikh S, Gipson G, Kennedy S . Innate PI3K p110δ regulates Th1/Th17 development and microbiota-dependent colitis. J Immunol. 2014; 192(8):3958-68. PMC: 3992276. DOI: 10.4049/jimmunol.1301533. View