Browse > Article
http://dx.doi.org/10.5187/jast.2022.e49

Gene expression profiling after ochratoxin A treatment in small intestinal epithelial cells from pigs  

Jung Woong, Yoon (Department of Animal Science and Biotechnology, Kyungpook National University)
Sang In, Lee (Department of Animal Science and Biotechnology, Kyungpook National University)
Publication Information
Journal of Animal Science and Technology / v.64, no.5, 2022 , pp. 842-853 More about this Journal
Abstract
Ochratoxin A (OTA) is a well-known mycotoxin that causes disease through the ingestion of contaminated food or feed, for example, in the porcine industry. The intestinal epithelium acts as the first barrier against food contamination. We conducted a study on the exposure of the porcine intestinal epithelium to OTA. We used the intestinal porcine epithelial cell line IPEC-J2 as an in vitro model to evaluate the altered molecular mechanisms following OTA exposure. Gene expression profiling revealed that OTA upregulated 782 genes and downregulated 896, totalling 1678 differentially expressed genes. Furthermore, immunofluorescence, quantitative real-time polymerase chain reaction, and western blotting confirmed that OTA damages the tight junction protein ZO-1. Moreover, OTA activated the expression of inflammatory genes (IL-6, IL-8, IL-10, NF-kB, TLR4, and TNF-α). In summary, this study confirmed that OTA alters various molecular mechanisms and has several adverse effects on IPEC-J2 cells.
Keywords
Intestinal porcine epithelial cell line (IPEC)-J2 cells; Ochratoxin A; Gene expression profiling; Tight junction protein; Inflammation;
Citations & Related Records
Times Cited By KSCI : 2  (Citation Analysis)
연도 인용수 순위
1 Peng M, Liu J, Liang Z. Probiotic Bacillus subtilis CW14 reduces disruption of the epithelial  barrier and toxicity of ochratoxin A to Caco-2 cells. Food Chem Toxicol. 2019;126:25-33.  https://doi.org/10.1016/j.fct.2019.02.009    DOI
2 Gao Y, Ye Q, Bao X, Huang X, Wang J, Zheng N. Transcriptomic and proteomic profiling  reveals the intestinal immunotoxicity induced by aflatoxin M1 and ochratoxin A. Toxicon.  2020;180:49-61. https://doi.org/10.1016/j.toxicon.2020.03.008    DOI
3 Rodriguez A, Rodriguez M, Martin A, Delgado J, Cordoba JJ. Presence of ochratoxin A on  the surface of dry-cured Iberian ham after initial fungal growth in the drying stage. Meat Sci.  2012;92:728-34. https://doi.org/10.1016/j.meatsci.2012.06.029    DOI
4 Battacone G, Nudda A, Pulina G. Effects of ochratoxin a on livestock production. Toxins.  2010;2:1796-824. https://doi.org/10.3390/toxins2071796    DOI
5 Brosnahan AJ, Brown DR. Porcine IPEC-J2 intestinal epithelial cells in microbiological  investigations. Vet Microbiol. 2012;156:229-37. https://doi.org/10.1016/j.vetmic.2011.10.017    DOI
6 Vergauwen H. The IPEC-J2 cell line. In: Verhoeckx K, Cotter P, Lopez-Exposito I, Kleiveland  C, Lea T, Mackie A, Requena T, Swiatecka D, Wichers H, editors. The impact of food  bioactives on health: in vitro and ex vivo models. Cham: Springer; 2015. p. 125-34. 
7 Rao X, Huang X, Zhou Z, Lin X. An improvement of the 2ˆ(-delta delta CT) method for  quantitative real-time polymerase chain reaction data analysis. Biostat Bioinforma Biomath.  2013;3:71-85. 
8 Marin DE, Pistol GC, Gras M, Palade M, Taranu I. A comparison between the effects of  ochratoxin A and aristolochic acid on the inflammation and oxidative stress in the liver and  kidney of weanling piglets. Naunyn-Schmiedebergs Arch Pharmacol. 2018;391:1147-56.  https://doi.org/10.1007/s00210-018-1538-9    DOI
9 Duerr CU, Hornef MW. The mammalian intestinal epithelium as integral player in the  establishment and maintenance of host-microbial homeostasis. Semin Immunol. 2012;24:25-35. https://doi.org/10.1016/j.smim.2011.11.002    DOI
10 Blikslager AT, Moeser AJ, Gookin JL, Jones SL, Odle J. Restoration of barrier function  in injured intestinal mucosa. Physiol Rev. 2007;87:545-64. https://doi.org/10.1152/  physrev.00012.2006    DOI
11 Wang H, Chen Y, Zhai N, Chen X, Gan F, Li H, et al. Ochratoxin A-induced apoptosis of  IPEC-J2 cells through ROS-mediated mitochondrial permeability transition pore opening  pathway. J Agric Food Chem. 2017;65:10630-7. https://doi.org/10.1021/acs.jafc.7b04434    DOI
12 Heinemann U, Schuetz A. Structural features of tight-junction proteins. Int J Mol Sci.  2019;20:6020. https://doi.org/10.3390/ijms20236020    DOI
13 Lee SI, Kim IH. Nucleotide-mediated SPDEF modulates TFF3-mediated wound healing  and intestinal barrier function during the weaning process. Sci Rep. 2018;8:4827. https://doi.org/10.1038/s41598-018-23218-4    DOI
14 Basler K, Brandner JM. Tight junctions in skin inflammation. Pflugers Arch. 2017;469:3-14.  https://doi.org/10.1007/s00424-016-1903-9    DOI
15 Bhat AA, Uppada S, Achkar IW, Hashem S, Yadav SK, Shanmugakonar M, et al. Tight  junction proteins and signaling pathways in cancer and inflammation: a functional crosstalk.   Front Physiol. 2019;9:1942. https://doi.org/10.3389/fphys.2018.01942    DOI
16 Zhang JM, An J. Cytokines, inflammation, and pain. Int Anesthesiol Clin. 2007;45:27-37.  https://doi.org/10.1097/AIA.0b013e318034194e    DOI
17 Villarino AV, Kanno Y, O'Shea JJ. Mechanisms and consequences of Jak-STAT signaling in  the immune system. Nat Immunol. 2017;18:374-84. https://doi.org/10.1038/ni.3691    DOI
18 Jung K, Miyazaki A, Hu H, Saif LJ. Susceptibility of porcine IPEC-J2 intestinal epithelial  cells to infection with porcine deltacoronavirus (PDCoV) and serum cytokine responses of  gnotobiotic pigs to acute infection with IPEC-J2 cell culture-passaged PDCoV. Vet Microbiol.  2018;221:49-58. https://doi.org/10.1016/j.vetmic.2018.05.019    DOI
19 Doyle SL, O'Neill LAJ. Toll-like receptors: from the discovery of NFκB to new insights into  transcriptional regulations in innate immunity. Biochem Pharmacol. 2006;72:1102-13. https://doi.org/10.1016/j.bcp.2006.07.010    DOI
20 Ayoub S, Berberi A, Fayyad-Kazan M. Cytokines, masticatory muscle inflammation, and pain:  an update. J Mol Neurosci. 2020;70:790-5. https://doi.org/10.1007/s12031-020-01491-1    DOI
21 Iwasaki A, Medzhitov R. Control of adaptive immunity by the innate immune system. Nat  Immunol. 2015;16:343-53. https://doi.org/10.1038/ni.3123    DOI
22 Kawai T, Akira S. Signaling to NF-κB by toll-like receptors. Trends Mol Med. 2007;13:460-9.  https://doi.org/10.1016/j.molmed.2007.09.002    DOI
23 Lee SI, Kim HS, Koo JM, Kim IH. Lactobacillus acidophilus modulates inflammatory activity  by regulating the TLR4 and NF-κB expression in porcine peripheral blood mononuclear  cells after lipopolysaccharide challenge. Br J Nutr. 2016;115:567-75. https://doi.org/10.1017/S0007114515004857    DOI
24 Dolcet X, Llobet D, Pallares J, Matias-Guiu X. NF-kB in development and progression of  human cancer. Virchows Arch. 2005;446:475-82. https://doi.org/10.1007/s00428-005-1264-9   DOI
25 Rodrigues I, Naehrer K. A three-year survey on the worldwide occurrence of mycotoxins in  feedstuffs and feed. Toxins. 2012;4:663-75. https://doi.org/10.3390/toxins4090663    DOI
26 Ceci E, Bozzo G, Bonerba E, Di Pinto A, Tantillo MG. Ochratoxin A detection by HPLC in  target tissues of swine and cytological and histological analysis. Food Chem. 2007;105:364-8.  https://doi.org/10.1016/j.foodchem.2006.12.019    DOI
27 O'Brien E, Dietrich DR. Ochratoxin A: the continuing enigma. Crit Rev Toxicol. 2005;35:33-60. https://doi.org/10.1080/10408440590905948    DOI
28 Yang C, Song G, Lim W. Effects of mycotoxin-contaminated feed on farm animals. J Hazard  Mater. 2020;389:122087. https://doi.org/10.1016/j.jhazmat.2020.122087    DOI
29 Duarte SC, Lino CM, Pena A. Ochratoxin A in feed of food-producing animals: an  undesirable mycotoxin with health and performance effects. Vet Microbiol. 2011;154:1-13.  https://doi.org/10.1016/j.vetmic.2011.05.006    DOI
30 Tao Y, Xie S, Xu F, Liu A, Wang Y, Chen D, et al. Ochratoxin A: toxicity, oxidative stress and  metabolism. Food Chem Toxicol. 2018;112:320-31. https://doi.org/10.1016/j.fct.2018.01.002    DOI
31 Marin DE, Pistol GC, Gras MA, Palade ML, Taranu I. Comparative effect of ochratoxin A  on inflammation and oxidative stress parameters in gut and kidney of piglets. Regul Toxicol  Pharmacol. 2017;89:224-31. https://doi.org/10.1016/j.yrtph.2017.07.031    DOI
32 Wang H, Zhai N, Chen Y, Fu C, Huang K. OTA induces intestinal epithelial barrier  dysfunction and tight junction disruption in IPEC-J2 cells through ROS/Ca2+-mediated MLCK activation. Environ Pollut. 2018;242:106-12. https://doi.org/10.1016/j.envpol.2018.06.062    DOI
33 Jennings-Gee JE, Tozlovanu M, Manderville R, Miller MS, Pfohl-Leszkowicz A, Schwartz  GG. Ochratoxin A: in utero exposure in mice induces adducts in testicular DNA. Toxins.  2010;2:1428-44. https://doi.org/10.3390/toxins2061428    DOI
34 Ringot D, Chango A, Schneider YJ, Larondelle Y. Toxicokinetics and toxicodynamics of  ochratoxin A, an update. Chem Biol Interact. 2006;159:18-46. https://doi.org/10.1016/j.cbi.2005.10.106    DOI
35 Gao Y, Meng L, Liu H, Wang J, Zheng N. The compromised intestinal barrier induced by  mycotoxins. Toxins. 2020;12:619. https://doi.org/10.3390/toxins12100619    DOI
36 Lee B, Moon KM, Kim CY. Tight junction in the intestinal epithelium: its association with  diseases and regulation by phytochemicals. J Immunol Res. 2018;2018:2645465. https://doi.org/10.1155/2018/2645465    DOI
37 Chen Y, Wang H, Zhai N, Wang C, Huang K, Pan C. Nontoxic concentrations of OTA  aggravate DON-induced intestinal barrier dysfunction in IPEC-J2 cells via activation  of NF-κB signaling pathway. Toxicol Lett. 2019;311:114-24. https://doi.org/10.1016/j.toxlet.2019.04.021    DOI
38 Wang W, Zhai S, Xia Y, Wang H, Ruan D, Zhou T, et al. Ochratoxin A induces liver  inflammation: involvement of intestinal microbiota. Microbiome. 2019;7:151. https://doi.org/10.1186/s40168-019-0761-z    DOI
39 Stoev SD, Anguelov G, Ivanov I, Pavlov D. Influence of ochratoxin A and an extract  of artichoke on the vaccinal immunity and health in broiler chicks. Exp Toxicol Pathol.  2000;52:43-55. https://doi.org/10.1016/S0940-2993(00)80014-7    DOI