doi: 10.15389/agrobiology.2021.4.664eng
UDC: 636.52.58:619:616-099:575
Acknowledgements:
Supported financially from the Russian Science Foundation, grant No. 20-76-10003
EFFECT OF T-2 TOXIN ON EXPRESSION OF GENES ASSOCIATED WITH IMMUNITY IN TISSUES OF THE BLIND PROCESSES OF THE INTESTINAL AND PANCREAS OF BROILERS (Gallus gallus L.)
E.A. Yildirim1 ✉, A.A. Grozina2, V.G. Vertiprakhov2 ✉, L.A. Ilyina1,
V.A. Filippova1, G.Yu. Laptev1, E.A. Brazhnik1, K.A. Kalitkina1,
N.V. Tarlavin1, A.V. Dubrovin1, N.I. Novikova1, D.G. Tyurina1
1JSC Biotrof+, 19, korp. 1, Zagrebskii bulv., St. Petersburg, 192284 Russia, e-mail deniz@biotrof.ru (✉ corresponding author), ilina@biotrof.ru, dumova@biotrof.ru, laptev@biotrof.ru, bea@biotrof.ru, kseniya.k.a@biotrof.ru, tarlav1995@biotrof.ru, dubrovin@biotrof.ru, novikova@biotrof.ru, tiurina@biotrof.ru;
2Federal Scientific Center All-Russian Research and Technological Poultry Institute RAS, 10, ul. Ptitsegradskaya, Sergiev Posad, Moscow Province, 141311 Russia, e-mail alena_fisinina@mail.ru, Vertiprakhov63@mail.ru (✉ corresponding author)
ORCID:
Yildirim E.A. orcid.org/0000-0002-5846-4844
Brazhnik E.A. orcid.org/0000-0003-2178-9330
Grozina A.A. orcid.org/0000-0002-3088-0454
Kalitkina K.A. orcid.org/0000-0002-9541-6839
Vertiprakhov V.G. orcid.org/0000-0002-3240-7636
Tarlavin N.V. orcid.org/0000-0002-6474-9171
Ilyina L.A. orcid.org/0000-0003-2490-6942
Dubrovin A.V. orcid.org/0000-0001-8424-4114
Filippova V.A. orcid.org/0000-0001-8789-9837
Novikova N.I. orcid.org/0000-0002-9647-4184
Laptev G.Yu. orcid.org/0000-0002-8795-6659
Tyurina D.G. orcid.org/0000-0001-9001-2432
Received April 22, 2021
A significant proportion of poultry feed is contaminated with T-2 toxin. The bird’s immune system is one of the targets of this xenobiotic. However, the results of studying the effect of T-2 toxin on the expression of immunity genes in birds are extremely limited. In the present study, we have shown that contamination of broiler feed with T-2 toxin affects the level of expression of genes associated with the functioning of the immune system in the cecum and pancreas. The aim of the work was to assess the effect of T-2 toxin on the level of expression of genes involved in the immune system responses in the tissues of the intestine and pancreas cecum in broilers. The feeding trials with T-2 toxin added to the feed were carried out on broilers of the Smena 8 cross from 30 to 50 days of age (the vivarium of the Federal Research Center VNITIP RAS, 2020). Broilers were assigned to four treatments. The control group I received a diet with no T-2 toxin added, group II received a diet added with 100 μg/kg T-2 toxin, group III with 200 μg/kg, and group IV with 400 μg/kg. Gene expression was analyzed by quantitative PCR with reverse transcription (RT-qPCR). A reverse transcription reaction was performed to generate cDNA on an RNA template using the iScript™ Reverse Transcription Supermix (Bio-Rad, USA). The following primer pairs were used: for Interleukin 6 (IL6) F — 5′-AGGACGAGATGTGCAAGAAGTTC-3′, R — 5′-TTG-GGCAGGTTGAGGTTGTT-3′; for Interleukin 8 (IL8) F — 5′-GGAAGAGAGGTGTGCTTGGA-3′, R — 5′-TAAC-ATGAGGCACCGA-TGTG-3′; for Interferon 7 (IRF7) F — 5′-ATCCCTTGGAAGCACAACGCC-3′, R — 5′-CTGA-GGCAACCGCGTAGACCTT-3′; for Prostaglandin-endoperoxide synthase 2 (PTGS2) F — 5′-TC-GAGATCACACTTGATTGACA-3′, R — 5′-TTTGTGCCTTGTGGGTCAG-3′; for avian beta-defensin 9 (AvBD9(Gal9)) F — 5′-AACACCGTCAGGCATCTTCACA-3′, R — 5′-CGTCTTCTTGGCTGTAAGCTGGA-3′, for avian beta-defensin 10 (AvBD10(Gal10)) F — 5′-GCTCTTCGCT-GTTCTCC-TCT-3′, R — 5′-CCAGAGATGGTGAAGGTG-3′; for Caspase 6 (Casp6) F — 5′-CAG-AGGAGACAAGTGCCAGA-3′, R — 5′-CCAGGAGCCGTTTACAGTTT-3′. The beta-actin protein gene was a reference control. Amplification reactions were performed using a SsoAdvanced™ Universal SYBR® Green Supermix (Bio-Rad, USA). The amplification mode and conditions corresponded to those proposed by the primer developers. The relative expression level was estimated by the 2-ΔΔCT method. Biochemical blood profiles of broilers were analyzed (a Sinnowa BS3000P semi-automatic biochemical analyzer, SINNOWA Medical Science & Technology Co., Ltd, China) with a set of veterinary diagnostic reagents (DIAKON-VET, Russia). Principal component analysis (PCA) was used to compare gene expression levels and blood biochemical parameters. The expression of genes associated with the inflammatory response, apoptosis, antimicrobial and antiviral protection was evaluated. Activation (p ≤ 0.05) of the expression of the pro-inflammatory genes IL6 and PTGS2 occurred in broilers fed T-2 toxin. This can adversely affect the health and productivity of the birds, since the overproduction of proinflammatory cytokines is involved in the pathogenesis of several diseases. An increase (up to 41.7-fold, p = 0.0005) in the PTGS2gene expression in the pancreas was characteristic of all groups fed T-2 toxin compared to the control. In the tissues of the intestinal cecum, there was a decrease (up to 12.5-fold, p = 0.02) in the expression level of the Casp6 gene of the apoptosis factor regardless of the T-2 toxin dosage. In the pancreas, there was a reverse tendency of a sharp increase in the Casp6 gene expression as the T-2 toxin concentration increased (p ≤ 0.0008). In group II, the expression increased 22.4 times (p = 0.0008), in group III 715.8 times (p = 0.0003), in group IV 31288.3 times (p = 0.0003) compared to the control. The expression of AvBD9 and AvBD10 genes of avian β-defensins which are associated with a higher bacteriostatic activity against many pathogens decreased 2.1 to 5.3 times (p ≤ 0.05) in the caecum of broilers fed 200 and 400 200 μg/kg T-2 toxin. In the pancreas, regardless of the T-2 toxin dosage, on the contrary, the expression of these genes significantly increased (p ≤ 0.04). In the caecum, 100 μg/kg T-2 toxin exposure inhibited the IRF7 gene expression 3-fold (p = 0.03) compared to the control. This can negative affect birds’ health, since the IRF7 gene of the interferon regulatory factor 7 participates in counteraction against many viruses. In general, the pancreas was found to be more sensitive to the effects of the T-2 toxin because the expression of almost all studied genes was significantly increased as compared to that in the cecum tissue. This difference in the immune response may be due to the functional divergence between the intestine and the pancreas. PCA method revealed a close relationship between the expression of the PTGS2 gene in the pancreas, the IL6, PTGS2, IL8, IRF7, AvBD9, AvBD10, and Casp6 genes in the cecum and the total blood protein, trypsin, glucose, alkaline phosphatase, triglycerides, and phosphatase/trypsin coefficient. Our findings indicate the effect of feed contamination with T-2 toxin on the immunological functions of the caecum and pancreas of broilers through modulation of the immunity genes expression. Quantitative PCR analysis of the expression of immunity genes can serve as an effective tool for the search for predictive markers of T-2 toxicosis of poultry to monitor the health status of livestock in poultry farms.
Keywords: T-2 toxin, mycotoxicosis, broilers, gene expression, bird immunity, cytokine, interferon, apoptosis, β-defensins.
REFERENCES
- Adhikari M., Negi B., Kaushik N., Adhikari A., Al-Khedhairy A.A., Kaushik N.K., Ha Choi E. T-2 mycotoxin: toxicological effects and decontamination strategies. Oncotarget, 2017, 16(8): 33933-33952 CrossRef
- Creppy E.E. Update of survey, regulation and toxic effects of mycotoxins in Europe. Toxicology Letters, 2002, 127(1-3): 19-28 CrossRef
- Bezborodova N.A. Monitoring mikotoksinov v kormakh i kormovom syr'e i kliniko-immunologicheskie osobennosti mikotoksikozov zhivotnykh v Ural'skom regione. Avtoreferat kandidatskoi dissertatsii [Monitoring of mycotoxins in feeds and feed raw materials and clinical and immunological features of animal mycotoxicosis in the Ural region. PhD Thesis]. Ekaterinburg, 2009 (in Russ.).
- Gogina N.N. Materialy XVIII Mezhdunarodnoi konferentsii Vsemirnoi nauchnoi assotsiatsii po ptitsevodstvu (Rossiiskoe otdelenie) «Innovatsionnoe obespechenie yaichnogo i myasnogo ptitsevodstva Rossii» [Proc. Int. Conf. of World’s Poultry Science Association (Russian branch) «Innovative provision of egg and meat poultry farming in Russia»]. NP «Nauchnyi tsentr po ptitsevodstvu», p. Rzhavki, 2015: 127-129 (in Russ.).
- Kononenko G.P., Burkin A.A., Zotova E.V. Veterinariya segodnya, 2020, 3(34): 213-219 CrossRef (in Russ.).
- Oswald I.P., Marin D.E., Bouhet S., Pinton P., Taranu I., Accensi F. Immunotoxicological risk of mycotoxins for domestic animals. Food Additives and Contaminants, 2005, 22(4): 354-360 CrossRef
- Wan Q., Wu G., He Q., Tang H., Wang Y. The toxicity of acute exposure to T-2 toxin evaluated by the metabonomics technique. Molecular bioSystems, 2015, 11(3): 882-891 CrossRef
- Akande K.E., Abubakar M.M., Adegbola T.A., Bogoro S.E. Nutritional and health implications of mycotoxins in animal feeds: a review. Pakistan Journal of Nutrition, 2006, 5: 398-403 CrossRef
- Maresca M., Mahfoud R., Garmy N., Fantini J. The mycotoxin deoxynivalenol affects nutrient absorption in human intestinal epithelial cells. The Journal of Nutrition, 2002, 132(9): 2723-2731 CrossRef
- Sergent T., Parys M., Garsou S., Pussemier L., Schneider Y.-J., Larondelle Y. Deoxynivalenol transport across human intestinal Caco-2 cells and its effects on cellular metabolism at realistic intestinal concentrations. Toxicology Letters, 2006, 164(2): 167-176 CrossRef
- Pang V.F., Adams J.H., Beasley V.R., Buck W.B., Haschek W.M. Myocardial and pancreatic lesions induced by T-2 toxin, a trichothecene mycotoxin, in swine. Veterinary Pathology, 1986, 23(3): 310-319 CrossRef
- Seeboth J., Solinhac R., Oswald I.P., Guzylack-Piriou L. The fungal T-2 toxin alters the activation of primary macrophages induced by TLR-agonists resulting in a decrease of the inflammatory response in the pig. Veterinary Research, 2012, 43(1): 35 CrossRef
- Pierron A., Alassane-Kpembi I., Oswald I.P. Impact of mycotoxin on immune response and consequences for pig health. Animal nutrition (Zhongguo xu mu shou yi xue hui), 2016, 2(2): 63-68 CrossRef
- Oswald I.P. Role of intestinal epithelial cells in the innate immune defence of the pig intestine. Veterinary Research, 2006, 37(3): 359-368 CrossRef
- Nochi T., Jansen C.A., Toyomizu M., van Eden W. The well-developed mucosal immune systems of birds and mammals allow for similar approaches of mucosal vaccination in both types of animals. Frontiers in Nutrition, 2018, 5: 60 CrossRef
- Casteleyn C., Doom M., Lambrechts E., Van den Broeck W., Simoens P., Cornillie P. Locations of gut-associated lymphoid tissue in the 3-month-old chicken: a review. Avian Pathology,2010, 39(3): 143-150 CrossRef
- Bar-Shira E., Sklan D., Friedman A. Establishment of immune competence in the avian GALT during the immediate post-hatch period. Developmental and Comparative Immunology, 2003, 27(2): 147-157 CrossRef
- Goitsuka R., Chen C.-L.H., Benyon L., Asano Y., Kitamura D., Cooper M.D. Chicken cathelicidin-B1, an antimicrobial guardian at the mucosal M cell gateway. Proceedings of the National Academy of Sciences of the United States of America, 2007, 104(38): 15063-15068 CrossRef
- Nile C.J., Townes C.L., Michailidis G., Hirst B.H., Hall J. Identification of chicken lysozyme g2 and its expression in the intestine. Cellular and Molecular Life Sciences, 2004, 61(21): 2760-2766. CrossRef
- Cuperus T., van Dijk A., Dwars R.M., Haagsman H.P. Localization and developmental expression of two chicken host defense peptides: cathelicidin-2 and avian β-defensin 9. Developmental and Comparative Immunology, 2016, 61: 48-59 CrossRef
- Gibson M.S., Kaiser P., Fife M. The chicken IL-1 family: evolution in the context of the studied vertebrate lineage. Immunogenetics, 2014, 66(7-8): 427-438 CrossRef
- Klotman M.E., Chang T.L. Defensins in innate antiviral immunity. Nature Reviews Immunology, 2006, 6(6): 447-456 CrossRef
- Lynn D.J., Higgs R., Gaines S., Tierney J., James T., Lloyd A.T., Fares M.A., Mulcahy G., O’Farrelly C. Bioinformatic discovery and initial characterisation of nine novel antimicrobial peptide genes in the chicken. Immunogenetics, 2004, 56(3): 170-177 CrossRef
- Yacoub H.A., Elazzazy A.M., Abuzinadah O.A.H., Al-Hejin A.M., Mahmoud M.M., Harakeh S.M. Antimicrobial activities of chicken β-defensin (4 and 10) peptides against pathogenic bacteria and fungi. Frontiers in Cellular and infection Microbiology, 2015, 5: 36 CrossRef
- Cuperus T., Coorens M., van Dijk A., Haagsman H.P. Avian host defense peptides. Developmental and Comparative Immunology, 2013, 41(3): 352-369 CrossRef
- Kapczuk P., Kosik-Bogacka D., Kupnicka P., Metryka E., Simińska D., Rogulska K., Skórka M., Gutowska I., Chlubek D., Baranowska-Bosiacka I. The influence of selected gastrointestinal parasites on apoptosis in intestinal epithelial cells. Biomolecules, 2020, 10(5): 674 CrossRef
- Xue C.Y., Wang G.H., Chen F., Zhang X.B., Bi Y.Z., Cao Y.C. Immunopathological effects of ochratoxin A and T-2 toxin combination on broilers. Poultry Science, 2010, 89(6): 1162-1166 CrossRef
- Zeka F., Vanderheyden K., Smet E., Cuvelier C., Mestdagh P., Vandesompele J. Straightforward and sensitive RT-qPCR based gene expression analysis of FFPE samples. Scientific Reports, 2016, 6: 21418 CrossRef
- Meza Cerda M.I., Gray R., Higgins D.P. Cytokine RT-qPCR and ddPCR for immunological investigations of the endangered Australian sea lion (Neophoca cinerea) and other mammals. PeerJ, 2020, 8: e10306 CrossRef
- Laptev G.Y., Filippova V.A., Kochish I.I., Yildirim E.A., Ilina L.A., Dubrovin A.V., Brazhnik E.A., Novikova N.I., Novikova O.B., Dmitrieva M.E., Smolensky V.I., Surai P.F., Griffin D.K., Romanov M.N. Examination of the expression of immunity genes and bacterial profiles in the caecum of growing chickens infected with Salmonella enteritidis and fed a phytobiotic. Animals, 2019, 9(9): 615 CrossRef
- Livak K.J., Schmittgen T.D. Analysis of relative gene expression data using real-time quantitative PCR and the 2-ΔΔCT method. Methods, 2001, 25(4): 402-408 CrossRef
- Jolliffe I.T. Principal component analysis. Springer series in statistics. New York, Springer-Verlag, 2002 CrossRef
- Brown S., Wilburn W., Martin T., Whalen M. Butyltin compounds alter secretion of interleukin 6 from human immune cells. Journal of Applied Toxicology, 2018, 38(2): 201-218 CrossRef
- Moldawer L.L., Gelin J., Scherstén T., Lundholm K.G.. Circulating interleukin 1 and tumor necrosis factor during inflammation. The American Journal of Physiology, 1987, 253(6): 922-928 CrossRef
- Cannon J.G., Tompkins R.G., Gelfand J.A., Michie H.R., Stanford G.G., van der Meer J.W., Endres S., Lonnemann G., Corsetti J., Chernow B. Circulating IL-1 and TNF in septic shock and experimental endotoxin fever. Journal of Infectious Diseases, 1990, 161(1): 79-84 CrossRef
- Lotze A.T.M. The cytokine handbook. Academic Press, 2003.
- Broom L.J., Kogut M.H. Inflammation: friend or foe for animal production? Poultry Science, 2018, 97(2): 510-514. CrossRef
- Moldawer L.L., Andersson C., Gelin J., Lundholm K.G. Regulation of food intake and hepatic protein synthesis by recombinant-derived cytokines. American Journal of Physiology, 1988, 254(3): 450-456 CrossRef
- Tracey K.J., Wei H., Manogue K.R., Fong Y., Hesse D.G., Nguyen H.T., Kuo G.C., Beutler B., Cotran R.S., Cerami A. Cachectin/tumor necrosis factor induces cachexia, anemia, and inflammation. Journal of Experimental Medicine, 1988, 167(3): 1211-1227 CrossRef
- Fong Y., Moldawer L.L., Marano M., Wei H., Barber A., Manogue K., Tracey K.J., Kuo G. Cachectin/TNF or IL-1 alpha induces cachexia with redistribution of body proteins. American Journal of Physiology, 1989, 256(3-Pt 2): R659-665 CrossRef
- Prescott S.M., Fitzpatrick F.A. Cyclooxygenase-2 and carcinogenesis. Biochimica et Biophysica Acta, 2000, 1470(2): 69-78 CrossRef
- Thuresson E.D., Lakkides K.M., Rieke C.J., Sun Y., Wingerd B.A., Micielli R., Mulichak A.M., Malkowski M.G., Garavito R.M., Smith W.L. Prostaglandin Endoperoxide H Synthase-1: the functions of cyclooxygenase active site residues in the binding, positioning, and oxygenation of arachidonic acid 210. Journal of Biological Chemistry, 2001, 276(13): 10347-10357 CrossRef
- Yan H., Takamoto M., Sugane K. Exposure to Bisphenol A prenatally or in adulthood promotes T(H)2 cytokine production associated with reduction of CD4CD25 regulatory T cells. Environmental Health Perspectives, 2008, 116(4): 514-519 CrossRef
- Kuo C.-H., Hsieh C.-C., Kuo H.-F., Huang M.-Y., Yang S.-N., Chen L.-C., Huang S.-K., Hung C.-H. Phthalates suppress type I interferon in human plasmacytoid dendritic cells via epigenetic regulation. Allergy, 2013, 68(7): 870-879 CrossRef
- Feng Y., Tian J., Xie H.Q., She J., Xu S.L., Xu T., Tian W., Fu H., Li S., Tao W., Wang L., Chen Y., Zhang S., Zhang W., Guo T.L., Zhao B. Effects of acute low-dose exposure to the chlorinated flame retardant Dechlorane 602 and Th1 and Th2 immune responses in adult male mice. Environmental Health Perspectives, 2016, 124(9): 1406-1413 CrossRef
- Pestka J.J., Zhou H.-R., Moon Y., Chung Y.J. Cellular and molecular mechanisms for immune modulation by deoxynivalenol and other trichothecenes: unraveling a paradox. Toxicology Letters, 2004, 153(1): 61-73 CrossRef
- Alnemri E.S., Livingston. D.J., Nicholson D.W., Salvesen G., Thornberry N.A., Wong W.W., Yuan J. Human ICE/CED-3 protease nomenclature. Cell, 1996, 87: 171 CrossRef
- Krammer P.H. CD95’s deadly mission in the immune system. Nature, 2000, 407(6805): 789-795 CrossRef
- Savino W., Dardenne M. Neuroendocrine control of thymus physiology. Endocrine Reviews, 2000, 21(4): 412-443 CrossRef
- Lv Q.-Y., Wan B., Guo L.-H., Zhao L., Yang Y. In vitro immune toxicity of polybrominated diphenyl ethers on murine peritoneal macrophages: apoptosis and immune cell dysfunction. Chemosphere, 2015, 120: 621-630 CrossRef
- Wu B., Guo H., Cui H., Peng X., Fang J., Zuo Z., Deng J., Wang X., Huang J. Pathway underlying small intestine apoptosis by dietary nickel chloride in broiler chickens. Chemico-biological Interactions, 2016, 243: 91-106 CrossRef
- Huang F.-M., Chang Y.-C., Lee S.-S., Ho Y.-C., Yang M.-L., Lin H.-W., Kuan Y.-H. Bisphenol A exhibits cytotoxic or genotoxic potential via oxidative stress-associated mitochondrial apoptotic pathway in murine macrophages. Food and Chemical Toxicology, 2018, 122: 215-224 CrossRef
- Hwang J.K., Min K.H., Choi K.H., Hwang Y.C., Jeong I.-K., Ahn K.J., Chung H.-Y., Chang J.S. Bisphenol A reduces differentiation and stimulates apoptosis of osteoclasts and osteoblasts. Life Sciences, 2013, 93(9-11): 367-372 CrossRef
- Neri M., Virzì G.M., Brocca A., Garzotto F., Kim J.C., Ramponi F., de Cal M., Lorenzin A., Brendolan A., Nalesso F., Zanella M., Ronco C. In vitro cytotoxicity of Bisphenol A in monocytes cell line. Blood Purification, 2015, 40(2): 180-186 CrossRef
- Mokra K., Kocia M., Michałowicz J. Bisphenol A and its analogs exhibit different apoptotic potential in peripheral blood mononuclear cells (in vitro study). Food and Chemical Toxicology, 2015, 84: 79-88 CrossRef
- Baker A.H., Wu T.H., Bolt A.M., Gerstenfeld L.C., Mann K.K., Schlezinger J.J. From the cover: tributyltin alters the bone marrow microenvironment and suppresses B cell development. Toxicological Sciences, 2017, 158(1): 63-75 CrossRef
- Miura K., Aminova L., Murayama Y. Fusarenon-X induced apoptosis in HL-60 cells depends on caspase activation and cytochrome c release. Toxicology, 2002, 172(2): 103-112 CrossRef
- Nagase M., Shiota T., Tsushima A., Murshedul Alam M., Fukuoka S., Yoshizawa T., Sakato N. Molecular mechanism of satratoxin-induced apoptosis in HL-60 cells: activation of caspase-8 and caspase-9 is involved in activation of caspase-3. Immunology Letters, 2002, 84(1): 23-27 CrossRef
- Pae H.O., Oh G.S., Choi B.M., Seo E.A., Oh H., Shin M.K., Kim T.H., Kwon T.O., Chunga H.T. Induction of apoptosis by 4-acetyl-12,13-epoxyl-9-trichothecene-3,15-diol from Isaria japonica Yasuda through intracellular reactive oxygen species formation and caspase-3 activation in human leukemia HL-60 cells. Toxicology in vitro, 2003, 17(1): 49-57 CrossRef
- Ihara T., Yamamoto T., Sugamata M., Okumura H., Ueno Y. The process of ultrastructural changes from nuclei to apoptotic body. Virchows Archiv, 1998, 433(5): 443-447 CrossRef
- Islam Z., Nagase M., Ota A., Ueda S., Yoshizawa T., Sakato N. Structure-function relationship of T-2 toxin and its metabolites in inducing thymic apoptosis in vivo in mice. Bioscience, Biotechnology, and Biochemistry, 1998, 62(8): 1492-1497 CrossRef
- van Dijk A., Veldhuizen E.J.A., Haagsman H.P. Avian defensins. Veterinary Immunology and Immunopathology, 2008, 124(1-2): 1-18 CrossRef
- Chertov O., Michiel D.F., Xu L., Wang J.M., Tani K., Murphy W.J., Longo D.L., Taub D.D., Oppenheim J.J. Identification of defensin-1, defensin-2, and CAP37/azurocidin as T-cell chemoattractant proteins released from interleukin-8-stimulated neutrophils. Journal of Biological Chemistry, 1996, 271(6): 2935-2940 CrossRef
- Yang D., Chertov O., Bykovskaia S.N., Chen Q., Buffo M.J., Shogan J., Anderson M., Schröder J.M., Wang J.M., Howard O.M., Oppenheim J.J. Beta-defensins: linking innate and adaptive immunity through dendritic and T cell CCR6. Science, 1999, 286(5439): 525-528 CrossRef
- Niyonsaba F., Iwabuchi K., Matsuda H., Ogawa H., Nagaoka I. Epithelial cell-derived human beta-defensin-2 acts as a chemotaxin for mast cells through a pertussis toxin-sensitive and phospholipase C-dependent pathway. International Immunology, 2002, 14(4): 421-426 CrossRef
- Gupta S., Jindal N., Khokhar R.S., Asrani R.K., Ledoux D.R., Rottinghaus G.E. Individual and combined effects of ochratoxin A and Salmonella enterica serovar Gallinarum infection on pathological changes in broiler chickens. Avian Pathology, 2008, 37(3): 265-272 CrossRef
- Elissalde M.H., Ziprin R.L., Huff W.E., Kubena L.F., Harvey R.B. Effect of ochratoxin A on Salmonella-challenged broiler chicks. Poultry Science, 1994, 73(8): 1241-1248 CrossRef
- Oswald I.P., Desautels C., Laffitte J., Fournout S., Peres S.Y., Odin M., Le Bars P., Le Bars J., Fairbrother J.M. Mycotoxin fumonisin B1 increases intestinal colonization by pathogenic Escherichia coli in pigs. Applied and Environmental Microbiology, 2003, 69(10): 5870-5874 CrossRef
- Verbrugghe E., Vandenbroucke V., Dhaenens M., Shearer N., Goossens J., De Saeger S., Eeckhout M., D’Herde K., Thompson A., Deforce D., Boyen F., Leyman B., Van Parys A., De Backer P., Haesebrouck F., Croubels S., Pasmans F. T-2 toxin induced Salmonella typhimurium intoxication results in decreased Salmonella numbers in the cecum contents of pigs, despite marked effects on Salmonella-host cell interactions. Veterinary Research, 2012, 43(1): 22 CrossRef
- Ning S., Pagano J.S., Barber G.N. IRF7: activation, regulation, modification and function. Genes and Immunity, 2011, 12(6): 399-414 CrossRef
- Wang Y., Yang F., Yin H., He Q., Lu Y., Zhu Q., Lan X., Zhao X., Li D., Liu Y, Xu H. Chicken interferon regulatory factor 7 (IRF7) can control ALV-J virus infection by triggering type I interferon production through affecting genes related with innate immune signaling pathway. Developmental & Comparative Immunology, 2021, 119(5573): 104026 CrossRef
- Haller O., Kochs G., Weber F. The interferon response circuit: induction and suppression by pathogenic viruses. Virology, 2006, 344(1): 119-130 CrossRef
- Lessard M., Savard C., Deschene K., Lauzon K., Pinilla V.A., Gagnon C.A., Lapointe J., Guay F., Chorfi Y. Impact of deoxynivalenol (DON) contaminated feed on intestinal integrity and immune response in swine. Food and Chemical Toxicology, 2015, 80: 7-16 CrossRef
- Nascimento A.A., Sales A., Cardoso T.R.D., Pinheiro N.L., Mendes R.M.M. Immunocytochemical study of the distribuition of endocrine cells in the pancreas of the Brazilian sparrow species Zonotrichia capensis subtorquata (Swaison, 1837). Brazilian Journal of Biology, 2007, 67(4): 735-740 CrossRef
- Scaglia L., Cahill C.J., Finegood D.T., Bonner-Weir S. Apoptosis participates in the remodeling of the endocrine pancreas in the neonatal rat. Endocrinology, 1997, 138(4): 1736-1741 CrossRef
- Petrik J., Arany E., McDonald T.J., Hill D.J. Apoptosis in the pancreatic islet cells of the neonatal rat is associated with a reduced expression of insulin-like growth factor II that may act as a survival factor. Endocrinology, 1998, 139(6): 2994-3004 CrossRef
- Adams J.M., Low M.J. Gene expression profiling reveals a possible role for somatostatin in the innate immune response of the liver. Genomics Data, 2015, 5: 42-45 CrossRef
- Malmstrøm M.L., Hansen M.B., Andersen A.M., Ersbøll A.K., Nielsen O.H., Jørgensen L.N., Novovic S. Cytokines and organ failure in acute pancreatitis: inflammatory response in acute pancreatitis. Pancreas, 2012, 41(2): 271-277 CrossRef
- Al-Zghoul M.B., Alliftawi A.R.S., Saleh K.M.M., Jaradat Z.W. Expression of digestive enzyme and intestinal transporter genes during chronic heat stress in the thermally manipulated broiler chicken. Poultry Science, 2019, 98(9): 4113-4122 CrossRef
- Saluja A., Saluja M., Villa A., Leli U., Rutledge P., Meldolesi J., Steer M. Pancreatic duct obstruction in rabbits causes digestive zymogen and lysosomal enzyme colocalization. Journal of Clinical Investigation, 1989, 84(4): 1260-1266 CrossRef
- Saluja A.K., Bhagat L., Lee H.S., Bhatia M., Frossard J.L., Steer M.L. Secretagogue-induced digestive enzyme activation and cell injury in rat pancreatic acini. American Journal of Physiology, 1999, 276(4): 835-842 CrossRef
- Dixit A., Dawra R.K., Dudeja V., Saluja A.K. Role of trypsinogen activation in genesis of pancreatitis. Pancreapedia: Exocrine Pancreas Knowledge Base, 2016 CrossRef
- Kisselev A.F., Garcia-Calvo M., Overkleeft H.S., Peterson E., Pennington M.W., Ploegh H.L., Thornberry N.A., Goldberg A.L. The caspase-like sites of proteasomes, their substrate specificity, new inhibitors and substrates, and allosteric interactions with the trypsin-like sites. Journal of Biological Chemistry, 2003, 278(38): 35869-35877 CrossRef
- Tang X.-E., Li H., Chen L.-Y., Xia X.-D., Zhao Z.-W., Zheng X.-L., Zhao G.-J., Tang C.-K. IL-8 negatively regulates ABCA1 expression and cholesterol efflux via upregulating miR-183 in THP-1 macrophage-derived foam cells. Cytokine, 2019, 122: 154385 CrossRef
- Varshney P., Narasimhan A., Mittal S., Malik G., Sardana K., Saini N. Transcriptome profiling unveils the role of cholesterol in IL-17A signaling in psoriasis. Scientific Reports, 2016, 6: 19295 CrossRef