Українська English

ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2015; 61(5): 57-64

Expression of aryl hydrocarbon receptor and ATG16L1 protein in experimental oxazolone-induced colitis in rats

A.S. Zherebiatiev, A.M. Kamyshny

    Zaporozhye State Medical University, Zaporozhye, Ukraine


We studied the expression of AhR and ATG16L1 protein in experimental oxazolone-induced colitis in rats and anti-inflammatory action of recombinant antagonist of IL-1 receptors (ARIL-1) and simvastatin. The immunopositive cells were determined using an indirect immunofluorescence technique with using a monoclonal rat antibody. It has been established that development of colitis was accompanied by an increase of total number of ATG16L1+-lymphocytes (by 30%, P <0.05) in lymphoid structures of the colon. However, the amount of AhR+-lymphocytes has not changed. At the same time has increased the concentration of ATG16L1 protein (by 4-11%, P <0.05) in immunopositive cells. Administration of simvastatin and ARIL-1 during the development of experimental pathology was accompanied by decrease of total number of AhR+ (by 24-38%, P <0.05) and ATG16L1+-lymphocytes (by 43% - 2 fold, P <0.05) in the colon.

Keywords: colitis; recombinant antagonist of receptors of interleukin-1 (ARIL-1); simvastatin; aryl hydrocarbon receptor; autophagy related 16-like 1 protein.


  1. Kaser A, Zeissig S, Blumberg RS. Inflammatory bowel disease. Annu Rev Immunol.2010;28:573-621. CrossRef PubMed PubMedCentral
  3. Monteleone I, MacDonald TT, Pallone F, Monteleone G. The aryl hydrocarbon receptor in inflammatory bowel disease: linking the environment to disease pathogenesis. Curr Opin Gastroenterol. 2012 ;28(4):310-3. CrossRef PubMed
  5. Ray SS, Swanson HI. Dioxin-induced immortalization of normal human keratinocytes and silencing of p53 and p16INK4a. J Biol Chem. 2004 ;279(26):27187-93. CrossRef PubMed
  7. Marlowe JL, Fan Y, Chang X, Peng L, Knudsen ES, Xia Y, et al. The aryl hydrocarbon receptor binds to E2F1 and inhibits E2F1-induced apoptosis. Mol Biol Cell. 2008;19(8):3263-71. CrossRef PubMed PubMedCentral
  9. Shimada T, Hiramatsu N, Hayakawa K, Takahashi S, Kasai A, Tagawa Y, et al. Dual suppression of adipogenesis by cigarette smoke through activation of the aryl hydrocarbon receptor and induction of endoplasmic reticulum stress. Am J Physiol Endocrinol Metab. 2009;296(4):E721-30.
  11. Høyer-Hansen M, Jäättelä M. Connecting endoplasmic reticulum stress to autophagy by unfolded protein response and calcium. Cell Death Differ. 2007;14(9):1576-82. CrossRef PubMed
  13. Hampe J, Franke A, Rosenstiel P, Till A, Teuber M, Huse K, et al. A genome-wide association scan of nonsynonymous SNPs identifies a susceptibility variant for Crohn disease in ATG16L1. Nat Genet. 2007;39(2):207-11. CrossRef PubMed
  15. Mizushima N, Kuma A, Kobayashi Y, Yamamoto A, Matsubae M, Takao T, et al. Mouse Apg16L, a novel WD-repeat protein, targets to the autophagic isolation membrane with the Apg12-Apg5 conjugate. J Cell Sci. 2003;116(Pt 9):1679-88.
  17. Bobin-Dubigeon C, Collin X, Grimaud N, Robert JM, Le Baut G, Petit JY. Effects of tumour necrosis factor-alpha synthesis inhibitors on rat trinitrobenzene sulphonic acid-induced chronic colitis. Eur J Pharmacol. 2001;431(1):103-10. CrossRef  
  18. Boirivant M, Fuss IJ, Chu A, Strober W. Oxazolone colitis: A murine model of T helper cell type 2 colitis treatable with antibodies to interleukin 4. J Exp Med. 1998;188(10):1929-39. CrossRef PubMed PubMedCentral
  20. Furumatsu K, Nishiumi S, Kawano Y, Ooi M, Yoshie T, Shiomi Y, et al. A role of the aryl hydrocarbon receptor in attenuation of colitis. Dig Dis Sci. 2011;56(9):2532-44. CrossRef PubMed
  22. Murthy A, Li Y, Peng I, Reichelt M, Katakam AK, Noubade R, et al. A Crohn's disease variant in Atg16l1 enhances its degradation by caspase 3. Nature. 2014;506(7489):456-62. CrossRef PubMed
  24. Saitoh T, Fujita N, Jang MH, Uematsu S, Yang BG, Satoh T, et al. Loss of the autophagy protein Atg16L1 enhances endotoxin-induced IL-1beta production. Nature. 2008;456(7219):264-8. CrossRef PubMed
  26. Cadwell K, Patel KK, Maloney NS, Liu TC, Ng AC, Storer CE, et al. Virus-plus-susceptibility gene interaction determines Crohn's disease gene Atg16L1 phenotypes in intestine. Cell. 2010;141(7):1135-45. CrossRef PubMed PubMedCentral
  28. Maher BM, Dhonnchu TN, Burke JP, Soo A, Wood AE, Watson RW. Statins alter neutrophil migration by modulating cellular Rho activity--a potential mechanism for statins-mediated pleotropic effects? J Leukoc Biol. 2009;85(1):186-93. CrossRef PubMed
  30. Jahovic N, Gedik N, Ercan F, Sirvanci S, Yüksel M, Sener G, et al. Effects of statins on experimental colitis in normocholesterolemic rats. Scand J Gastroenterol. 2006;41(8):954-62. CrossRef PubMed
  32. Lee JY, Kim JS, Kim JM, Kim N, Jung HC, Song IS. Simvastatin inhibits NF-kappaB signaling in intestinal epithelial cells and ameliorates acute murine colitis. Int Immunopharmacol. 2007;7(2):241-8. CrossRef PubMed
  34. Youngman KR, Simon PL, West GA, Cominelli F, Rachmilewitz D, Klein JS, et al. Localization of intestinal interleukin 1 activity and protein and gene expression to lamina propria cells. Gastroenterology. 1993;104(3):749-58. CrossRef  
  35. Tountas NA, Casini-Raggi V, Yang H, Di Giovine FS, Vecchi M, Kam L, et al. Functional and ethnic association of allele 2 of the interleukin-1 receptor antagonist gene in ulcerative colitis. Gastroenterology. 1999;117(4):806-13. CrossRef  

© National Academy of Sciences of Ukraine, Bogomoletz Institute of Physiology, 2014-2024.