An Adenosine A3 Receptor Agonist Inhibits DSS-induced Colitis in Mice Through Modulation of the NF-κB Signaling Pathway

Overview

Journal Sci Rep

Specialty Science

Date 2015 Mar 13

PMID 25762375

Citations 26

Authors

Tianhua Ren

Ting Tian

Xiao Feng

Shicai Ye

Hao Wang

Weiyun Wu

Yumei Qiu

Caiyuan Yu

Yanting He

Juncheng Zeng

Junwei Cen

Yu Zhou

Affiliations

Soon will be listed here.

Abstract

The role of the adenosine A3 receptor (A3AR) in experimental colitis is controversial. The A3AR agonist N(6)-(3-iodobenzyl)adenosine-5'-N-methyluronamide (IB-MECA) has been shown to have a clinical benefit, although studies in A3AR-deficient mice suggest a pro-inflammatory role. However, there are no studies on the effect of 2-Cl-IB-MECA and the molecular mechanism of action of A3AR in murine colitis models in vivo. Is it the same as that observed in vitro? The interaction between 2-CL-IB-MECA and A3AR in a murine colitis model and the signaling pathways associated with this interaction remain unclear. Here we demonstrate a role for the NF-κB signaling pathway and its effect on modifying the activity of proinflammatory factors in A3AR-mediated biological processes. Our results demonstrated that A3AR activation possessed marked effects on experimental colitis through the NF-κB signaling pathway.

Citing Articles

Investigation of Metabolites in Fermented Wheat Bran and Its Bio Function in Alleviating Colitis in Mice Model.

Agista A, Chien Y, Koseki T, Nagaoka H, Ohnuma T, Ohsaki Y Metabolites. 2024; 14(7).

PMID: 39057682 PMC: 11278778. DOI: 10.3390/metabo14070359.

Namodenoson at the Crossroad of Metabolic Dysfunction-Associated Steatohepatitis and Hepatocellular Carcinoma.

Etzion O, Bareket-Samish A, Yardeni D, Fishman P Biomedicines. 2024; 12(4).

PMID: 38672201 PMC: 11047856. DOI: 10.3390/biomedicines12040848.

Adenosine receptors differentially mediate enteric glial cell death induced by Toxins A and B.

Costa D, Shin J, Goldbeck S, Bolick D, Mesquita F, Loureiro A Front Immunol. 2023; 13:956326.

PMID: 36726986 PMC: 9885079. DOI: 10.3389/fimmu.2022.956326.

Drugs Targeting the A3 Adenosine Receptor: Human Clinical Study Data.

Fishman P Molecules. 2022; 27(12).

PMID: 35744805 PMC: 9229414. DOI: 10.3390/molecules27123680.

Cancer biology and molecular genetics of A adenosine receptor.

Mazziotta C, Rotondo J, Lanzillotti C, Campione G, Martini F, Tognon M Oncogene. 2021; 41(3):301-308.

PMID: 34750517 PMC: 8755539. DOI: 10.1038/s41388-021-02090-z.

References

Rhee L, Murphy S, Kolodziej L, Grimm W, Weber C, Lodolce J . Expression of TNFAIP3 in intestinal epithelial cells protects from DSS- but not TNBS-induced colitis. Am J Physiol Gastrointest Liver Physiol. 2012; 303(2):G220-7. PMC: 3404569. DOI: 10.1152/ajpgi.00077.2012. View

Martin L, Pingle S, Hallam D, Rybak L, Ramkumar V . Activation of the adenosine A3 receptor in RAW 264.7 cells inhibits lipopolysaccharide-stimulated tumor necrosis factor-alpha release by reducing calcium-dependent activation of nuclear factor-kappaB and extracellular signal-regulated kinase 1/2. J Pharmacol Exp Ther. 2005; 316(1):71-8. DOI: 10.1124/jpet.105.091868. View

Spehlmann M, Eckmann L . Nuclear factor-kappa B in intestinal protection and destruction. Curr Opin Gastroenterol. 2009; 25(2):92-9. DOI: 10.1097/MOG.0b013e328324f857. View

Hussain A, Gharanei A, Nagra A, Maddock H . Caspase inhibition via A3 adenosine receptors: a new cardioprotective mechanism against myocardial infarction. Cardiovasc Drugs Ther. 2013; 28(1):19-32. DOI: 10.1007/s10557-013-6500-y. View

Atreya I, Atreya R, Neurath M . NF-kappaB in inflammatory bowel disease. J Intern Med. 2008; 263(6):591-6. DOI: 10.1111/j.1365-2796.2008.01953.x. View

Dai C, Zheng C, Meng F, Zhou Z, Sang L, Jiang M . VSL#3 probiotics exerts the anti-inflammatory activity via PI3k/Akt and NF-κB pathway in rat model of DSS-induced colitis. Mol Cell Biochem. 2012; 374(1-2):1-11. DOI: 10.1007/s11010-012-1488-3. View

Michael S, Warstat C, Michel F, Yan L, Muller C, Nieber K . Adenosine A(2A) agonist and A(2B) antagonist mediate an inhibition of inflammation-induced contractile disturbance of a rat gastrointestinal preparation. Purinergic Signal. 2009; 6(1):117-24. PMC: 2837822. DOI: 10.1007/s11302-009-9174-y. View

Xue X, Ramakrishnan S, Anderson E, Taylor M, Zimmermann E, Spence J . Endothelial PAS domain protein 1 activates the inflammatory response in the intestinal epithelium to promote colitis in mice. Gastroenterology. 2013; 145(4):831-41. PMC: 3799890. DOI: 10.1053/j.gastro.2013.07.010. View

Satoh Y, Williams M, Habara Y . Effects of AIF4- and ATP on intracellular calcium dynamics of crypt epithelial cells in mouse small intestine. Cell Tissue Res. 1999; 298(2):295-305. DOI: 10.1007/s004419900069. View

10.

Vincenzi F, Targa M, Corciulo C, Gessi S, Merighi S, Setti S . Pulsed electromagnetic fields increased the anti-inflammatory effect of A₂A and A₃ adenosine receptors in human T/C-28a2 chondrocytes and hFOB 1.19 osteoblasts. PLoS One. 2013; 8(5):e65561. PMC: 3669296. DOI: 10.1371/journal.pone.0065561. View

11.

Ren T, Qiu Y, Wu W, Feng X, Ye S, Wang Z . Activation of adenosine A3 receptor alleviates TNF-α-induced inflammation through inhibition of the NF-κB signaling pathway in human colonic epithelial cells. Mediators Inflamm. 2014; 2014:818251. PMC: 4016939. DOI: 10.1155/2014/818251. View

12.

Antonioli L, Fornai M, Colucci R, Awwad O, Ghisu N, Tuccori M . Differential recruitment of high affinity A1 and A2A adenosine receptors in the control of colonic neuromuscular function in experimental colitis. Eur J Pharmacol. 2010; 650(2-3):639-49. DOI: 10.1016/j.ejphar.2010.10.041. View

13.

Wan F, Lenardo M . The nuclear signaling of NF-kappaB: current knowledge, new insights, and future perspectives. Cell Res. 2009; 20(1):24-33. PMC: 3052775. DOI: 10.1038/cr.2009.137. View

14.

Ren T, Grants I, Alhaj M, McKiernan M, Jacobson M, Hassanain H . Impact of disrupting adenosine A₃ receptors (A₃⁻/⁻ AR) on colonic motility or progression of colitis in the mouse. Inflamm Bowel Dis. 2011; 17(8):1698-713. PMC: 3116114. DOI: 10.1002/ibd.21553. View

15.

Ren W, Yin J, Wu M, Liu G, Yang G, Xion Y . Serum amino acids profile and the beneficial effects of L-arginine or L-glutamine supplementation in dextran sulfate sodium colitis. PLoS One. 2014; 9(2):e88335. PMC: 3914992. DOI: 10.1371/journal.pone.0088335. View

16.

Hassanian S, Dinarvand P, Rezaie A . Adenosine regulates the proinflammatory signaling function of thrombin in endothelial cells. J Cell Physiol. 2014; 229(9):1292-300. PMC: 4037378. DOI: 10.1002/jcp.24568. View

17.

Varani K, Vincenzi F, Tosi A, Targa M, Masieri F, Ongaro A . Expression and functional role of adenosine receptors in regulating inflammatory responses in human synoviocytes. Br J Pharmacol. 2010; 160(1):101-15. PMC: 2860211. DOI: 10.1111/j.1476-5381.2010.00667.x. View

18.

Hasko G, Linden J, Cronstein B, Pacher P . Adenosine receptors: therapeutic aspects for inflammatory and immune diseases. Nat Rev Drug Discov. 2008; 7(9):759-70. PMC: 2568887. DOI: 10.1038/nrd2638. View

19.

Kolachala V, Ruble B, Vijay-Kumar M, Wang L, Mwangi S, Figler H . Blockade of adenosine A2B receptors ameliorates murine colitis. Br J Pharmacol. 2008; 155(1):127-37. PMC: 2440087. DOI: 10.1038/bjp.2008.227. View

20.

Ochaion A, Bar-Yehuda S, Cohen S, Barer F, Patoka R, Amital H . The anti-inflammatory target A(3) adenosine receptor is over-expressed in rheumatoid arthritis, psoriasis and Crohn's disease. Cell Immunol. 2009; 258(2):115-22. DOI: 10.1016/j.cellimm.2009.03.020. View