Biological Trace Element Research

, Volume 185, Issue 1, pp 170–176 | Cite as

The Adverse Effects of Se Toxicity on Inflammatory and Immune Responses in Chicken Spleens

  • Yachao Wang
  • Li Jiang
  • Jian He
  • Mao Hu
  • Fankun Zeng
  • Yuanfeng Li
  • He Tian
  • Xuegang LuoEmail author


Selenium (Se) is an essential trace element, but excessive intake of Se could induce Se poisoning, and result in various health problems. NF-κB regulated many molecules of the immune response and the inflammatory response, and Th1/Th2 balance played a key in the regulation of immune response. The aim of this study is to investigate the role of NF-κB pathway and Th1/Th2 imbalance in the adverse influence of Se poisoning on chicken spleens. In the current study, 90 chickens were randomly divided into two groups (n = 45 per group). The chickens were maintained either on a basal diet (the control group) containing 0.2 mg/kg Se or a high supplemented diet (the Se group) containing 15 mg/kg Se for 45 days. Then, we observed the pathohistology of spleen cells and detected NO content, iNOS activity, and the expression of NF-κB, iNOS, COX-2, PTGE, IL-6, TNF-α, Foxp3, IL-4, and IFN-γ in chicken spleens. In chicken spleens of the Se group, the result showed typical characteristics of inflammation: the content of NO and the activity of iNOS were increased, and the expression of NF-κB, iNOS, COX-2, PTGE, IL-6, TNF-α, and IL-4 was enhanced and that of Foxp3 and IFN-γ was decreased. Our study showed that Se toxicity could promote inflammation via NF-κB pathway, impairing the immune function, and changing Th1/Th2 balance in the chicken spleens.


Chicken spleens Se toxicity Inflammation Immune response 



The authors thank the Elsevier English Language Editing System to correct grammatical, spelling, and other common errors.

Funding Information

The present work was financially supported by Southwest University of Science and Technology (15zx7121) and National Defense Basic Research Project (16zg6101).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no competing interests.


  1. 1.
    Xi J, Zhe X, Xia Z, Chen M, Xu S (2017) The antagonistic effect of selenium on Pb-induced apoptosis via mitochondrial dynamics pathway in the chicken kidney. Chemosphere 180:259–266CrossRefGoogle Scholar
  2. 2.
    Yao H, Fan R, Zhao X, Zhao W, Liu W, Yang J, Sattar H, Zhao J, Zhang Z, Xu S (2011) Selenoprotein W redox-regulated Ca2+ channels correlate with selenium deficiency-induced muscles Ca2+ leak. Oncotarget 7:57618Google Scholar
  3. 3.
    Yao HD, Wu Q, Zhang ZW, Li S, Wang XL, Lei XG, Xu SW (2013) Selenoprotein W serves as an antioxidant in chicken myoblasts. Biochim Biophys Acta 1830:3112–3120CrossRefPubMedGoogle Scholar
  4. 4.
    Yao HD, Wu Q, Zhang ZW, Zhang JL, Li S, Huang JQ, Ren FZ, Xu SW, Wang XL, Lei XG (2013) Gene expression of endoplasmic reticulum resident selenoproteins correlates with apoptosis in various muscles of se-deficient chicks. J Nutr 143(5):613–619. CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Qin H-b, Zhu J-m, Liang L, Wang M-s, Su H (2013) The bioavailability of selenium and risk assessment for human selenium poisoning in high-Se areas. China, Environ Int 52:66–74. CrossRefGoogle Scholar
  6. 6.
    Rayman MP (2000) The importance of selenium to human health. Lancet 356(9225):233–241. CrossRefPubMedGoogle Scholar
  7. 7.
    Arthur KBJ (2001) Selenium, selenoproteins and human health: a review. Public Health Nutr 4:593–599PubMedGoogle Scholar
  8. 8.
    Gad MA, Abd El-Twab SM (2009) Selenium toxicosis assessment (in vivo and in vitro) and the protective role of vitamin B12 in male quail (Coturnix Coturnix). Environ Toxicol Pharmacol 27(1):7–16. CrossRefPubMedGoogle Scholar
  9. 9.
    Spallholz JE, Palace VP, Reid TW (2004) Methioninase and selenomethionine but not Se-methylselenocysteine generate methylselenol and superoxide in an in vitro chemiluminescent assay: implications for the nutritional carcinostatic activity of selenoamino acids. Biochem Pharmacol 67(3):547–554. CrossRefPubMedGoogle Scholar
  10. 10.
    Abul-Hassan KS, Lehnert BE, Guant L, Walmsley R (2004) Abnormal DNA repair in selenium-treated human cells. Mutat Res/Genet Toxicol Environ Mutagen 565(1):45–51. CrossRefGoogle Scholar
  11. 11.
    Rengarajan J, Szabo SJ, Glimcher LH (2000) Transcriptional regulation of Th1/Th2 polarization. Immunol Today 21(10):479–483. CrossRefPubMedGoogle Scholar
  12. 12.
    Liu F, Wang X-Y, Zhou X-P, Liu Z-P, Song X-B, Wang Z-Y, Wang L (2017) Cd disrupts autophagic flux by inhibiting cytosolic Ca2+−dependent autophagosome-lysosome fusion in primary rat proximal tubular cells. Toxicology 383:13–23. CrossRefPubMedGoogle Scholar
  13. 13.
    Guo Y, Zhao P, Guo G, Hu Z, Tian L, Zhang K, Zhang W, Xing M (2015) The role of oxidative stress in gastrointestinal tract tissues induced by arsenic toxicity in cocks. Biol Trace Elem Res 168(2):490–499. CrossRefPubMedGoogle Scholar
  14. 14.
    Giacconi R, Costarelli L, Malavolta M, Cardelli M, Galeazzi R, Piacenza F, Gasparini N, Basso A, Mariani E, Fulop T (2015) Effect of ZIP2 Gln/Arg/Leu (rs2234632) polymorphism on zinc homeostasis and inflammatory response following zinc supplementation. Biofactors 41(6):414–423. CrossRefPubMedGoogle Scholar
  15. 15.
    Wang H, Li S, Teng X (2016) The antagonistic effect of selenium on Pb-induced inflammatory factors and heat shock proteins mRNA expression in chicken livers. Biol Trace Elem Res 171(2):437–444. CrossRefPubMedGoogle Scholar
  16. 16.
    Krocova Z, Macela A, Kroca M, Hernychova L (2000) The immunomodulatory effect(s) of Pb and Cd on the cells of immune system in vitro. Toxicol in Vitro 14(1):33–40. CrossRefPubMedGoogle Scholar
  17. 17.
    Ninkov M, Popov Aleksandrov A, Demenesku J, Mirkov I, Mileusnic D, Petrovic A, Grigorov I, Zolotarevski L, Tolinacki M, Kataranovski D, Brceski I, Kataranovski M (2015) Toxicity of oral Cd intake: impact on gut immunity. Toxicol Lett 237(2):89–99. CrossRefPubMedGoogle Scholar
  18. 18.
    Barrett CW, Singh K, Motley AK, Lintel MK, Matafonova E, Bradley AM, Ning W, Poindexter SV, Parang B, Reddy VK, Chaturvedi R, Fingleton BM, Washington MK, Wilson KT, Davies SS, Hill KE, Burk RF, Williams CS (2013) Dietary selenium deficiency exacerbates DSS-induced epithelial injury and AOM/DSS-induced tumorigenesis. PLoS One 8(7):e67845. CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Li X, Xing M, Chen M, Zhao J, Fan R, Zhao X, Cao C, Yang J, Zhang Z, Xu S (2017) Effects of selenium-Pb interaction on the gene expression of inflammatory factors and selenoproteins in chicken neutrophils. Ecotoxicol Environ Saf 139:447–453. CrossRefPubMedGoogle Scholar
  20. 20.
    Yu D, Zhang Z, Yao H, Li S, Xu S-W (2015) The role of selenoprotein W in inflammatory injury in chicken immune tissues and cultured splenic lymphocyte. Biometals 28(1):75–87. CrossRefPubMedGoogle Scholar
  21. 21.
    Khoso PA, Yang Z, Liu C, Li S (2015) Selenium deficiency downregulates selenoproteins and suppresses immune function in chicken thymus. Biol Trace Elem Res 167(1):48–55. CrossRefPubMedGoogle Scholar
  22. 22.
    Wang Y, Wang K, Huang H, Gu X, Teng X (2017) Alleviative effect of selenium on inflammatory damage caused by Pb via inhibiting inflammatory factors and heat shock proteins in chicken testes. Environ Sci Pollut Res 24(15):13405–13413. CrossRefGoogle Scholar
  23. 23.
    Yao H, Zhao W, Zhao X, Fan R, Khoso PA, Zhang Z, Liu W, Xu S (2014) Selenium deficiency mainly influences the gene expressions of antioxidative selenoproteins in chicken muscles. Biol Trace Elem Res 161(3):318–327. CrossRefPubMedGoogle Scholar
  24. 24.
    Pfaffl MW (2001) A new mathematical model for relative quantification in real-time RT–PCR. Nucleic Acids Res 29(9):e45. CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Mcadam E, Haboubi HN, Forrester G, Eltahir Z, Spencer-Harty S, Davies C, Griffiths AP, Baxter JN, Jenkins GJ (2012) Inducible nitric oxide synthase (iNOS) and nitric oxide (NO) are important mediators of reflux-induced cell signalling in esophageal cells. Carcinogenesis 33(11):2035–2043. CrossRefPubMedGoogle Scholar
  26. 26.
    Charalambous MP, Lightfoot T, Speirs V, Horgan K, Gooderham NJ (2009) Expression of COX-2, NF-κB-p65, NF-κB-p50 and IKKα in malignant and adjacent normal human colorectal tissue. Br J Cancer 101(1):106–115. CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Caamaño J, Hunter CA (2002) NF-κB family of transcription factors: central regulators of innate and adaptive immune functions. Clin Microbiol Rev 15(3):414–429. CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Wang Y-C, Hu Y-W, Sha Y-H, Gao J-J, Ma X, Li S-F, Zhao J-Y, Qiu Y-R, Lu J-B, Huang C, Zhao J-J, Zheng L, Wang Q (2015) Ox-LDL upregulates IL-6 expression by enhancing NF-κB in an IGF2-dependent manner in THP-1 macrophages. Inflammation 38(6):2116–2123. CrossRefPubMedGoogle Scholar
  29. 29.
    Chen C-C, Sun Y-T, Chen J-J, Chiu K-T (2000) TNF-α-induced cyclooxygenase-2 expression in human lung epithelial cells: involvement of the phospholipase C-γ2, protein kinase C-α, tyrosine kinase, NF-κB-inducing kinase, and I-κB kinase 1/2 pathway. J Immunol 165(5):2719–2728. CrossRefPubMedGoogle Scholar
  30. 30.
    Du Y, Zhu Y, Teng X, Zhang K, Teng X, Li S (2015) Toxicological effect of manganese on NF-κB/iNOS-COX-2 signaling pathway in chicken testes. Biol Trace Elem Res 168(1):227–234. CrossRefPubMedGoogle Scholar
  31. 31.
    Phuagkhaopong S, Ospondpant D, Kasemsuk T, Sibmooh N, Soodvilai S, Power C, Vivithanaporn P (2017) Cd-induced IL-6 and IL-8 expression and release from astrocytes are mediated by MAPK and NF-κB pathways. Neurotoxicology 60:82–91. CrossRefPubMedGoogle Scholar
  32. 32.
    Yang T, Cao C, Yang J, Liu T, Lei XG, Zhang Z, Xu S (2017) miR-200a-5p regulates myocardial necroptosis induced by Se deficiency via targeting RNF11. Redox Biol 15:159–169.
  33. 33.
    Sheng P-f, Jiang Y, Zhang Z-w, Zhang J-l, Li S, Zhang Z-q, Xu S-w (2014) The effect of Se-deficient diet on gene expression of inflammatory cytokines in chicken brain. Biometals 27(1):33–43. CrossRefPubMedGoogle Scholar
  34. 34.
    Bretscher PA (2014) On the mechanism determining the Th1/Th2 phenotype of an immune response, and its pertinence to strategies for the prevention, and treatment, of certain infectious diseases. Scand J Immunol 79(6):361–376. CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Iavicoli I, Marinaccio A, Castellino N, Carelli G (2004) Altered cytokine production in mice exposed to Pb acetate. Int J Immunopathol Pharmacol 17(2_suppl):97–102. CrossRefPubMedGoogle Scholar
  36. 36.
    Cho Y, Ahn KH, Back MJ, Choi JM, Ji JE, Won JH, Fu Z, Jang JM, Kim DK (2012) Age-related effects of sodium arsenite on splenocyte proliferation and Th1/Th2 cytokine production. Arch Pharm Res 35(2):375–382. CrossRefPubMedGoogle Scholar
  37. 37.
    Nie H, Zheng Y, Li R, Guo TB, He D, Fang L, Liu X, Xiao L, Chen X, Wan B (2013) Phosphorylation of FOXP3 controls regulatory T cell function and is inhibited by TNF-α in rheumatoid arthritis. Nat Med 19(3):322–328. CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Yachao Wang
    • 1
    • 2
  • Li Jiang
    • 1
  • Jian He
    • 1
  • Mao Hu
    • 1
  • Fankun Zeng
    • 1
  • Yuanfeng Li
    • 1
  • He Tian
    • 1
  • Xuegang Luo
    • 2
    • 3
    Email author
  1. 1.School of Life Science and EngineeringSouthwest University of Science and TechnologyMianyangChina
  2. 2.Engineering Research Center of Biomass Materials, Ministry of EducationSouthwest University of Science and TechnologyMianyangChina
  3. 3.School of Material Science and EngineeringSouthwest University of Science and TechnologyMianyangChina

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