Combined Effect of Deoxynivalenol (DON) and Porcine Circovirus Type 2 (Pcv2) on Inflammatory Cytokine mRNA Expression

. 2021 Jun 13 ; 13 (6) : . [epub] 20210613

Jazyk angličtina Země Švýcarsko Médium electronic

Typ dokumentu časopisecké články, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/pmid34199278

Grantová podpora
VT2019-2021 UHK CEP - Centrální evidence projektů
202010 China-CEEC Joint University Education Project
2016YFD0501207, 2016YFD0501009 National Key R & D Program
31972741, 31572576 NSFC
2016T90477 China Postdoctoral Science Foundation
FN HK 00179906 Ministry of Health of the Czech Republic

A host's immune system can be invaded by mycotoxin deoxynivalenol (DON) poisoning and porcine circovirus type 2 (PCV2) infections, which affect the host's natural immune function. Pro-inflammatory cytokines, IL-1β and IL-6, are important regulators in the process of natural immune response, which participate in inflammatory response and enhance immune-mediated tissue damage. Preliminary studies have shown that DON promotes PCV2 infection by activating the MAPK signaling pathway. Here, we explored whether the mRNA expression of IL-1β and IL-6, induced by the combination of DON and PCV2, would depend on the MAPK signaling pathway. Specific pharmacological antagonists U0126, SP600125 and SB203580, were used to inhibit the activities of ERK, JNK and p38 in the MAPK signaling pathway, respectively. Then, the mRNA expression of IL-1β and IL-6 in PK-15 cells was detected to explore the effect of the MAPK signaling pathway on IL-1β and IL-6 mRNA induced by DON and PCV2. The results showed that PK-15 cells treated with DON or PCV2 induced the mRNA expression of IL-1β and IL-6 in a time- and dose-dependent manner. The combination of DON and PCV2 has an additive effect on inducing the mRNA expression of IL-1β and IL-6. Additionally, both DON and PCV2 could induce the mRNA expression of IL-1β and IL-6 via the ERK and the p38 MAPK signal pathways, while PCV2 could induce it via the JNK signal pathway. Taken together, our results suggest that MAPKs play a contributory role in IL-1β and IL-6 mRNA expression when induced by both DON and PCV2.

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Polak-Śliwińska M., Paszczyk B. Trichothecenes in Food and Feed, Relevance to Human and Animal Health and Methods of Detection: A Systematic Review. Molecules. 2021;26:454. doi: 10.3390/molecules26020454. PubMed DOI PMC

Yang C., Song G., Lim W. Effects of mycotoxin-contaminated feed on farm animals. J. Hazard. Mater. 2020;389:122087. doi: 10.1016/j.jhazmat.2020.122087. PubMed DOI

Yao Y., Long M. The biological detoxification of deoxynivalenol: A review. Food Chem. Toxicol. 2020;145:111649. doi: 10.1016/j.fct.2020.111649. PubMed DOI

Peng Z., Chen L., Xiao J., Zhou X., Nüssler A.K., Liu L., Liu J., Yang W. Review of mechanisms of deoxynivalenol-induced anorexia: The role of gut microbiota. J. Appl. Toxicol. 2017;37:1021–1029. doi: 10.1002/jat.3475. PubMed DOI

Wu W., Zhang H. Role of tumor necrosis factor-α and interleukin-1β in anorexia induction following oral exposure to the trichothecene deoxynivalenol (vomitoxin) in the mouse. J. Toxicol. Sci. 2014;39:875–886. doi: 10.2131/jts.39.875. PubMed DOI

Wu Q., Yue J., Zhang H., Kuca K., Wu W. Anorexic responses to trichothecene deoxynivalenol and its congeners correspond to secretion of tumor necrosis factor-α and interleukin-1β. Environ. Toxicol. Pharmacol. 2020;77:103371. doi: 10.1016/j.etap.2020.103371. PubMed DOI

Carty M., Guy C., Bowie A.G. Detection of Viral Infections by Innate Immunity. Biochem. Pharmacol. 2021;183:114316. doi: 10.1016/j.bcp.2020.114316. PubMed DOI

Riahi I., Marquis V., Pérez-Vendrell A.M., Brufau J., Esteve-Garcia E., Ramos A.J. Effects of Deoxynivalenol-Contaminated Diets on Metabolic and Immunological Parameters in Broiler Chickens. Animals. 2021;11:147. doi: 10.3390/ani11010147. PubMed DOI PMC

Plata-Salaman C.R. Immunomodulators and feeding regulation: A humoral link between the immune and nervous systems. Brain Behav. Immun. 1989;3:193–213. doi: 10.1016/0889-1591(89)90036-6. PubMed DOI

Dantzer R., Kelley K.W. Twenty years of research on cytokine-induced sickness behavior. Brain Behav. Immun. 2007;21:153–160. doi: 10.1016/j.bbi.2006.09.006. PubMed DOI PMC

McCusker R.H., Kelley K.W. Immune-neural connections: How the immune system’s response to infectious agents influences behavior. J. Exp. Biol. 2013;216:84–98. doi: 10.1242/jeb.073411. PubMed DOI PMC

Chung Y.J., Yang G.H., Islam Z., Pestka J.J. Up-regulation of macrophage inflammatory protein-2 and complement 3A receptor by the trichothecenes deoxynivalenol and satratoxin G. Toxicology. 2003;186:51–65. doi: 10.1016/S0300-483X(02)00605-4. PubMed DOI

He K., Pan X., Zhou H.R., Pestka J.J. Modulation of inflammatory gene expression by the ribotoxin deoxynivalenol involves coordinate regulation of the transcriptome and translatome. Toxicol. Sci. 2013;131:153–163. doi: 10.1093/toxsci/kfs266. PubMed DOI PMC

Wong S.S., Zhou H.R., Marin-Martinez M.L., Brooks K., Pestka J.J. Modulation of IL-1beta, IL-6 and TNF-alpha secretion and mRNA expression by the trichothecene vomitoxin in the RAW 264.7 murine macrophage cell line. Food Chem. Toxicol. 1998;36:409–419. doi: 10.1016/S0278-6915(97)00167-1. PubMed DOI

Meng X.J. Porcine circovirus type 2 (PCV2): Pathogenesis and interaction with the immune system. Annu Rev. Anim. Biosci. 2013;1:43–64. doi: 10.1146/annurev-animal-031412-103720. PubMed DOI

Zhai S.L., Lu S.S., Wei W.K., Lv D.H., Wen X.H., Zhai Q., Chen Q.L., Sun Y.W., Xi Y. Reservoirs of Porcine Circoviruses: A Mini Review. Front. Vet. Sci. 2019;6:319. doi: 10.3389/fvets.2019.00319. PubMed DOI PMC

Segalés J. Porcine circovirus type 2 (PCV2) infections: Clinical signs, pathology and laboratory diagnosis. Virus Res. 2012;164:10–19. doi: 10.1016/j.virusres.2011.10.007. PubMed DOI

Yang S., Liu B., Yin S., Shang Y., Zhang X., Khan M.U.Z., Liu X., Cai J. Porcine Circovirus Type 2 Induces Single Immunoglobulin Interleukin-1 Related Receptor (SIGIRR) Downregulation to Promote Interleukin-1β Upregulation in Porcine Alveolar Macrophage. Viruses. 2019;11:1021. doi: 10.3390/v11111021. PubMed DOI PMC

Han J., Zhang S., Zhang Y., Chen M., Lv Y. Porcine circovirus type 2 increases interleukin-1beta and interleukin-10 production via the MyD88-NF-kappa B signaling pathway in porcine alveolar macrophages in vitro. J. Vet. Sci. 2017;18:183–191. doi: 10.4142/jvs.2017.18.2.183. PubMed DOI PMC

Sipos W., Duvigneau J.C., Willheim M., Schilcher F., Hartl R.T., Hofbauer G., Exel B., Pietschmann P., Schmoll F. Systemic cytokine profile in feeder pigs suffering from natural postweaning multisystemic wasting syndrome (PMWS) as determined by semiquantitative RT-PCR and flow cytometric intracellular cytokine detection. Vet. Immunol. Immunopathol. 2004;99:63–71. doi: 10.1016/j.vetimm.2004.01.001. PubMed DOI

Sui X., Kong N., Ye L., Han W., Zhou J., Zhang Q., He C., Pan H. p38 and JNK MAPK pathways control the balance of apoptosis and autophagy in response to chemotherapeutic agents. Cancer Lett. 2014;344:174–179. doi: 10.1016/j.canlet.2013.11.019. PubMed DOI

He Y., She H., Zhang T., Xu H., Cheng L., Yepes M., Zhao Y., Mao Z. p38 MAPK inhibits autophagy and promotes microglial inflammatory responses by phosphorylating ULK1. J. Cell Biol. 2018;217:315–328. doi: 10.1083/jcb.201701049. PubMed DOI PMC

Wu W., He K., Zhou H.R., Berthiller F., Adam G., Sugita-Konishi Y., Watanabe M., Krantis A., Durst T., Zhang H., et al. Effects of oral exposure to naturally-occurring and synthetic deoxynivalenol congeners on proinflammatory cytokine and chemokine mRNA expression in the mouse. Toxicol. Appl. Pharmacol. 2014;278:107–115. doi: 10.1016/j.taap.2014.04.016. PubMed DOI PMC

Wei L., Zhu Z., Wang J., Liu J. JNK and p38 mitogen-activated protein kinase pathways contribute to porcine circovirus type 2 infection. J. Virol. 2009;83:6039–6047. doi: 10.1128/JVI.00135-09. PubMed DOI PMC

Memiş E.Y., Yalçın S.S. Human milk mycotoxin contamination: Smoking exposure and breastfeeding problems. J. Matern. Fetal Neonatal Med. 2021;34:31–40. doi: 10.1080/14767058.2019.1586879. PubMed DOI

Cai G., Sun K., Xia S., Feng Z., Zou H., Gu J., Yuan Y., Zhu J., Liu Z., Bian J. Decrease in immune function and the role of mitogen-activated protein kinase (MAPK) overactivation in apoptosis during T lymphocytes activation induced by zearalenone, deoxynivalenol, and their combinations. Chemosphere. 2020;255:126999. doi: 10.1016/j.chemosphere.2020.126999. PubMed DOI

Pierron A., Mimoun S., Murate L.S., Loiseau N., Lippi Y., Bracarense A.P., Schatzmayr G., He J.W., Zhou T., Moll W.D., et al. Microbial biotransformation of DON: Molecular basis for reduced toxicity. Sci. Rep. 2016;6:29105. doi: 10.1038/srep29105. PubMed DOI PMC

Awad W., Ghareeb K., Böhm J., Zentek J. The toxicological impacts of the Fusarium mycotoxin, deoxynivalenol, in poultry flocks with special reference to immunotoxicity. Toxins. 2013;5:912–925. doi: 10.3390/toxins5050912. PubMed DOI PMC

Pestka J. Toxicological mechanisms and potential health effects of deoxynivalenol and nivalenol. World Mycotoxin J. 2010;3:323–347. doi: 10.3920/WMJ2010.1247. DOI

Hai-Lan C., Hong-Lian T., Jian Y., Manling S., Heyu F., Na K., Wenyue H., Si-Yu C., Ying-Yi W., Ting-Jun H. Inhibitory effect of polysaccharide of Sargassum weizhouense on PCV2 induced inflammation in mice by suppressing histone acetylation. Biomed. Pharmacother. 2019;112:108741. doi: 10.1016/j.biopha.2019.108741. PubMed DOI

Sugita-Konishi Y., Pestka J. Differential upregulation of TNF-alpha, IL-6, and IL-8 production by deoxynivalenol (vomitoxin) and other 8-ketotrichothecenes in a human macrophage model. J. Toxicol. Environ. Health A. 2001;64:619–636. doi: 10.1080/152873901753246223. PubMed DOI

Islam Z., Gray J.S., Pestka J.J. p38 Mitogen-activated protein kinase mediates IL-8 induction by the ribotoxin deoxynivalenol in human monocytes. Toxicol. Appl. Pharmacol. 2006;213:235–244. doi: 10.1016/j.taap.2005.11.001. PubMed DOI

Amuzie C.J., Harkema J.R., Pestka J. Tissue distribution and proinflammatory cytokine induction by the trichothecene deoxynivalenol in the mouse: Comparison of nasal vs. oral exposure. Toxicology. 2008;248:39–44. doi: 10.1016/j.tox.2008.03.005. PubMed DOI

Amuzie C.J., Shinozuka J., Pestka J. Induction of suppressors of cytokine signaling by the trichothecene deoxynivalenol in the mouse. Toxicol. Sci. 2009;111:277–287. doi: 10.1093/toxsci/kfp150. PubMed DOI PMC

Chung Y.J., Zhou H.R., Pestka J. Transcriptional and posttranscriptional roles for p38 mitogen-activated protein kinase in upregulation of TNF-alpha expression by deoxynivalenol (vomitoxin) Toxicol. Appl. Pharmacol. 2003;193:188–201. doi: 10.1016/S0041-008X(03)00299-0. PubMed DOI

Gray J.S., Pestka J. Transcriptional regulation of deoxynivalenol-induced IL-8 expression in human monocytes. Toxicol. Sci. 2007;99:502–511. doi: 10.1093/toxsci/kfm182. PubMed DOI

Zhu X., Bai J., Liu P., Wang X., Jiang P. Suppressor of cytokine signaling 3 plays an important role in porcine circovirus type 2 subclinical infection by downregulating proinflammatory responses. Sci. Rep. 2016;6:32538. doi: 10.1038/srep32538. PubMed DOI PMC

Chen H.L., Tan H.L., Yang J., Wei Y.Y., Hu T.J. Sargassum polysaccharide inhibits inflammatory response in PCV2 infected-RAW264.7 cells by regulating histone acetylation. Carbohydr. Polym. 2018;200:633–640. doi: 10.1016/j.carbpol.2018.06.060. PubMed DOI

Yang J., Tan H.L., Gu L.Y., Song M.L., Wu Y.Y., Peng J.B., Lan Z.B., Wei Y.Y., Hu T.J. Sophora subprosrate polysaccharide inhibited cytokine/chemokine secretion via suppression of histone acetylation modification and NF-κb activation in PCV2 infected swine alveolar macrophage. Pt AInt. J. Biol. Macromol. 2017;104:900–908. doi: 10.1016/j.ijbiomac.2017.06.102. PubMed DOI

Qian G., Liu D., Hu J., Gan F., Hou L., Chen X., Huang K. Ochratoxin A-induced autophagy in vitro and in vivo promotes porcine circovirus type 2 replication. Cell Death Dis. 2017;8:e2909. doi: 10.1038/cddis.2017.303. PubMed DOI PMC

Qian G., Liu D., Hou L., Hamid M., Chen X., Gan F., Song S., Huang K. Ochratoxin A induces cytoprotective autophagy via blocking AKT/mTOR signaling pathway in PK-15 cells. Food Chem. Toxicol. 2018;122:120–131. doi: 10.1016/j.fct.2018.09.070. PubMed DOI

Liu D., Ge L., Wang Q., Su J., Chen X., Wang C., Huang K. Low-level contamination of deoxynivalenol: A threat from environmental toxins to porcine epidemic diarrhea virus infection. Environ. Int. 2020;143:105949. doi: 10.1016/j.envint.2020.105949. PubMed DOI PMC

Bae H.K., Pestka J. Deoxynivalenol induces p38 interaction with the ribosome in monocytes and macrophages. Toxicol. Sci. 2008;105:59–66. doi: 10.1093/toxsci/kfn102. PubMed DOI PMC

Bae H.K., Gray J.S., Li M., Vines L., Kim J., Pestka J. Hematopoietic cell kinase associates with the 40S ribosomal subunit and mediates the ribotoxic stress response to deoxynivalenol in mononuclear phagocytes. Toxicol. Sci. 2010;115:444–452. doi: 10.1093/toxsci/kfq055. PubMed DOI PMC

Livak K.J., Schmittgen T.D. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001;25:402–408. doi: 10.1006/meth.2001.1262. PubMed DOI

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