Intestinal Alkaline Phosphatase (IAP, IAP Enhancer) Attenuates Intestinal Inflammation and Alleviates Insulin Resistance

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2022 Aug 12

PMID 35958560

Authors

Chenzhe Gao

Marwa Yagoub Farag Koko

Mingxing Ding

Weichen Hong

Jianping Li

Na Dong

Mizhou Hui

Affiliations

Soon will be listed here.

Abstract

In this study, we investigated the effects of intestinal alkaline phosphatase (IAP) in controlled intestinal inflammation and alleviated associated insulin resistance (IR). We also explored the possible underlying molecular mechanisms, showed the preventive effect of IAP on IR , and verified the dephosphorylation of IAP for the inhibition of intestinal inflammation . Furthermore, we examined the preventive role of IAP in IR induced by a high-fat diet in mice. We found that an IAP + IAP enhancer significantly ameliorated blood glucose, insulin, low-density lipoprotein, gut barrier function, inflammatory markers, and lipopolysaccharide (LPS) in serum. IAP could dephosphorylate LPS and nucleoside triphosphate in a pH-dependent manner . Firstly, LPS is inactivated by IAP and IAP reduces LPS-induced inflammation. Secondly, adenosine, a dephosphorylated product of adenosine triphosphate, elicited anti-inflammatory effects by binding to the A receptor, which inhibits NF-κB, TNF, and PI3K-Akt signalling pathways. Hence, IAP can be used as a natural anti-inflammatory agent to reduce intestinal inflammation-induced IR.

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References

Nagashimada M, Sawamoto K, Ni Y, Kitade H, Nagata N, Xu L . CX3CL1-CX3CR1 Signaling Deficiency Exacerbates Obesity-induced Inflammation and Insulin Resistance in Male Mice. Endocrinology. 2021; 162(6). DOI: 10.1210/endocr/bqab064. View

Pease J, Williams T . Tipping the balance: A biased nanobody antagonist of CCR3 with potential for the treatment of eosinophilic inflammation. J Allergy Clin Immunol. 2018; 143(2):552-553. DOI: 10.1016/j.jaci.2018.10.052. View

Al Nabhani Z, Berrebi D, Martinez-Vinson C, Montcuquet N, Madre C, Roy M . Nod2 Protects the Gut From Experimental Colitis Spreading to Small Intestine. J Crohns Colitis. 2019; 14(5):669-679. DOI: 10.1093/ecco-jcc/jjz196. View

Kamimura T, Isobe N, Yoshimura Y . Effects of inhibitors of transcription factors, nuclear factor-κB and activator protein 1, on the expression of proinflammatory cytokines and chemokines induced by stimulation with Toll-like receptor ligands in hen vaginal cells. Poult Sci. 2017; 96(3):723-730. DOI: 10.3382/ps/pew366. View

Zizzo M, Caldara G, Bellanca A, Nuzzo D, Di Carlo M, Serio R . Preventive effects of guanosine on intestinal inflammation in 2, 4-dinitrobenzene sulfonic acid (DNBS)-induced colitis in rats. Inflammopharmacology. 2018; 27(2):349-359. DOI: 10.1007/s10787-018-0506-9. View

Kusagaya H, Fujisawa T, Yamanaka K, Mori K, Hashimoto D, Enomoto N . Toll-like receptor-mediated airway IL-17C enhances epithelial host defense in an autocrine/paracrine manner. Am J Respir Cell Mol Biol. 2013; 50(1):30-9. DOI: 10.1165/rcmb.2013-0130OC. View

Beutler B, Rietschel E . Innate immune sensing and its roots: the story of endotoxin. Nat Rev Immunol. 2003; 3(2):169-76. DOI: 10.1038/nri1004. View

He C, Yu T, Shi Y, Ma C, Yang W, Fang L . MicroRNA 301A Promotes Intestinal Inflammation and Colitis-Associated Cancer Development by Inhibiting BTG1. Gastroenterology. 2017; 152(6):1434-1448.e15. DOI: 10.1053/j.gastro.2017.01.049. View

Gong J, Zhang L, Zhang Q, Li X, Xia X, Liu Y . Lentiviral Vector-Mediated SHC3 Silencing Exacerbates Oxidative Stress Injury in Nigral Dopamine Neurons by Regulating the PI3K-AKT-FoxO Signaling Pathway in Rats with Parkinson's Disease. Cell Physiol Biochem. 2018; 49(3):971-984. DOI: 10.1159/000493228. View

10.

Filipp D, Brabec T, Voboril M, Dobes J . Enteric α-defensins on the verge of intestinal immune tolerance and inflammation. Semin Cell Dev Biol. 2018; 88:138-146. DOI: 10.1016/j.semcdb.2018.01.007. View

11.

Ruehlmann J, Xiang R, Niethammer A, Ba Y, Pertl U, Dolman C . MIG (CXCL9) chemokine gene therapy combines with antibody-cytokine fusion protein to suppress growth and dissemination of murine colon carcinoma. Cancer Res. 2001; 61(23):8498-503. View

12.

Son D, Kabir S, Dong Y, Lee E, Adunyah S . Characteristics of chemokine signatures elicited by EGF and TNF in ovarian cancer cells. J Inflamm (Lond). 2013; 10(1):25. PMC: 3694479. DOI: 10.1186/1476-9255-10-25. View

13.

Bilski J, Mazur-Bialy A, Wojcik D, Zahradnik-Bilska J, Brzozowski B, Magierowski M . The Role of Intestinal Alkaline Phosphatase in Inflammatory Disorders of Gastrointestinal Tract. Mediators Inflamm. 2017; 2017:9074601. PMC: 5339520. DOI: 10.1155/2017/9074601. View

14.

Hamarneh S, Mohamed M, Economopoulos K, Morrison S, Phupitakphol T, Tantillo T . A novel approach to maintain gut mucosal integrity using an oral enzyme supplement. Ann Surg. 2014; 260(4):706-14. PMC: 5034572. DOI: 10.1097/SLA.0000000000000916. View

15.

Yu Y, Yu X, Ma J, Tong Y, Yao J . Effects of NVP-BEZ235 on the proliferation, migration, apoptosis and autophagy in HT-29 human colorectal adenocarcinoma cells. Int J Oncol. 2016; 49(1):285-93. DOI: 10.3892/ijo.2016.3507. View

16.

Sharma D, Malik A, Balakrishnan A, Malireddi R, Kanneganti T . RIPK3 Promotes Expression and Pyrin Inflammasome Activation via Modulation of mTOR Signaling. J Immunol. 2020; 205(10):2778-2785. PMC: 9447007. DOI: 10.4049/jimmunol.2000244. View

17.

Ravingerova T, carnicka S, Nemcekova M, Ledvenyiova V, Adameova A, Kelly T . PPAR-alpha activation as a preconditioning-like intervention in rats in vivo confers myocardial protection against acute ischaemia-reperfusion injury: involvement of PI3K-Akt. Can J Physiol Pharmacol. 2012; 90(8):1135-44. DOI: 10.1139/y2012-052. View

18.

Kong X, Liao Y, Zhou L, Zhang Y, Cheng J, Yuan Z . Hematopoietic Cell Kinase (HCK) Is Essential for NLRP3 Inflammasome Activation and Lipopolysaccharide-Induced Inflammatory Response . Front Pharmacol. 2020; 11:581011. PMC: 7523510. DOI: 10.3389/fphar.2020.581011. View

19.

Citi S . Intestinal barriers protect against disease. Science. 2018; 359(6380):1097-1098. DOI: 10.1126/science.aat0835. View

20.

Vicente-Manzanares M, Horwitz A . Cell migration: an overview. Methods Mol Biol. 2011; 769:1-24. DOI: 10.1007/978-1-61779-207-6_1. View