反刍动物应激反应中糖皮质激素对免疫系统的调节机理

doi:10.11843/j.issn.0366-6964.2017.05.001

摘要/Abstract

摘要：

糖皮质激素是一种强效抗炎物质，对免疫系统有着广泛的抑制作用。在应激反应中糖皮质激素可通过抑制细胞因子释放、诱导细胞凋亡以及影响免疫细胞分化和迁移等途径，调控家畜的免疫系统功能，减轻炎症反应的同时抑制了免疫系统功能，从而增加患病风险。本文从糖皮质激素受体的表达、对免疫细胞的影响及对细胞因子的调节3个方面阐述了反刍动物应激反应中糖皮质激素的免疫调节作用及其机理，旨在为相关研究提供科学依据。

关键词: 反刍动物, 应激, 免疫调节, 糖皮质激素, 细胞因子

Abstract:

Glucocorticoids are effective and powerful anti-inflammatory substances, and make a wide inhibition on immune system. Glucocorticoids can regulate the immune system of the livestock by inhibiting the release of cytokines, inducing apoptosis, affecting immune cell differentiation and migration during the stress response, and inhibiting the immune system function of the livestock while reducing the inflammatory response, thereby which increase the risk of illness. In this article, the regulation mechanism of glucocorticoids to immune in ruminants stress response were discussed, focusing on glucocorticoid receptors expression, immune cells function and cytokines regulation, aiming to provide some references for related studies.

Key words: ruminants, stress, immune regulation, glucocorticoids, cytokines

中图分类号:

S852.2

张千, 李发弟, 李飞. 反刍动物应激反应中糖皮质激素对免疫系统的调节机理[J]. 畜牧兽医学报, 2017, 48(5): 785-792.

ZHANG Qian, LI Fa-di, LI Fei. Regulation Mechanism of Glucocorticoids to Immune System in Ruminants Stress Response[J]. ACTA VETERINARIA ET ZOOTECHNICA SINICA, 2017, 48(5): 785-792.

参考文献

[1] OAKLEY R H, CIDLOWSKI J A. Cellular processing of the glucocorticoid receptor gene and protein: new mechanisms for generating tissue-specific actions of glucocorticoids[J]. J Biol Chem, 2011, 286(5): 3177-3184.
[2] 田青, 王洪荣, 王梦芝. 氢化可的松对奶牛乳腺上皮细胞酪蛋白合成的影响[J]. 畜牧兽医学报, 2014, 45(10): 1663-1670.
TIAN Q, WANG H R, WANG M Z. Effects of HYD on the synthesis of casein in mammary epithelial cells of holstein cows in vitro[J]. Acta Veterinaria et Zootechnica Sinica, 2014, 45(10): 1663-1670. (in Chinese)
[3] REICHARDT H M, HORSCH K, GRONE H, et al. Mammary gland development and lactation are controlled by different glucocorticoid receptor activities[J]. Eur J Endocrinol, 2001, 145(4): 519-527.
[4] OLLIER S, BEAUDOIN F, VANACKER N, et al. Effect of reducing milk production using a prolactin-release inhibitor or a glucocorticoid on metabolism and immune functions in cows subjected to acute nutritional stress[J]. J Dairy Sci, 2016, 99(12): 9949-9961.
[5] GLASER R, KIECOLT-GLASER J K. Stress-induced immune dysfunction: implications for health[J]. Nat Rev Immunol, 2005, 5(3): 243-251.
[6] RIVIER C, VALE W. Interaction of corticotropin-releasing factor and arginine vasopressin on adrenocorticotropin secretion in vivo[J]. Endocrinology, 1983, 113(3): 939-942.
[7] WATABE T, TANAKA K, KUMAGAE M, et al. Role of endogenous arginine vasopressin in potentiating corticotropin-releasing hormone-stimulated corticotropin secretion in man[J]. J Clin Endocrinol Metab, 1988, 66(6): 1132-1137.
[8] 李玮, 刘蕤, 马尧, 等. 重度冷应激对三河牛血液生化指标及相关基因表达的影响[J]. 畜牧兽医学报, 2015, 46(8): 1463-1470.
LI W, LIU R, MA R, et al. Effect of severe cold stress on blood biochemical parameters and related gene expression in sanhe cattle[J]. Acta Veterinaria et Zootechnica Sinica, 2015, 46(8): 1463-1470. (in Chinese)
[9] EVANS R M. The steroid and thyroid hormone receptor superfamily[J]. Science, 1988, 240(4854): 889-895.
[10] CHINENOV Y, ROGATSKY I. Glucocorticoids and the innate immune system: crosstalk with the toll-like receptor signaling network[J]. Mol Cell Endocrinol, 2007, 275(1-2): 30-42.
[11] DUFF G C, GALYEAN M L. Board-invited review: recent advances in management of highly stressed, newly received feedlot cattle[J]. J Anim Sci, 2007, 85(3): 823-840.
[12] FELDMAN S, WEIDENFELD J. Electrical stimulation of the dorsal hippocampus caused a long lasting inhibition of ACTH and adrenocortical responses to photic stimuli in freely moving rats[J]. Brain Res, 2001, 911(1): 22-26.
[13] CALDENHOVEN E, LIDEN J, WISSINK S, et al. Negative cross-talk between RelA and the glucocorticoid receptor: a possible mechanism for the antiinflammatory action of glucocorticoids[J]. Mol Endocrinol, 1995, 9(4): 401-412.
[14] PUJOLS L, MULLOL J, TORREGO A, et al. Glucocorticoid receptors in human airways[J]. Allergy, 2004, 59(10): 1042-1052.
[15] PRATT W B, TOFT D O. Regulation of signaling protein function and trafficking by the hsp90/hsp70-based chaperone machinery[J]. Exp Biol Med, 2003, 228(2): 111-133.
[16] DEJAGER L, VANDEVYVER S, PETTA I, et al. Dominance of the strongest: inflammatory cytokines versus glucocorticoids[J]. Cytokine Growth Factor Rev, 2014, 25(1): 21-33.
[17] BASCHANT U, TUCKERMANN J. The role of the glucocorticoid receptor in inflammation and immunity[J]. J Steroid Biochem Mol Biol, 2010, 120(2-3): 69-75.
[18] TURNER J D, SCHOTE A B, MACEDO J A, et al. Tissue specific glucocorticoid receptor expression, a role for alternative first exon usage[J]. Biochem Pharmacol, 2006, 72(11): 1529-1537.
[19] PERLMAN W R, WEBSTER M J, HERMAN M M, et al. Age-related differences in glucocorticoid receptor mRNA levels in the human brain[J]. Neurobiol Aging, 2007, 28(3): 447-458.
[20] JOHNSTON D, KENNY D A, KELLY A K, et al. Characterisation of haematological profiles and whole blood relative gene expression levels in Holstein-Friesian and Jersey bull calves undergoing gradual weaning[J]. Animal, 2016, 10(9): 1547-1556.
[21] NEWTON R, LEIGH R, GIEMBYCZ M A. Pharmacological strategies for improving the efficacy and therapeutic ratio of glucocorticoids in inflammatory lung diseases[J]. Pharmacol Ther, 2010, 125(2): 286-327.
[22] HARR M W, RONG Y P, BOOTMAN M D, et al. Glucocorticoid-mediated inhibition of Lck modulates the pattern of T cell receptor-induced calcium signals by down-regulating inositol 1, 4, 5-trisphosphate receptors[J]. J Biol Chem, 2009, 284(46): 31860-31871.
[23] LWENBERG M, STAHN C, HOMMES D W, et al. Novel insights into mechanisms of glucocorticoid action and the development of new glucocorticoid receptor ligands[J]. Steroids, 2008, 73(9-10): 1025-1029.
[24] O'LOUGHLIN A, MCGEE M, WATERS S M, et al. Examination of the bovine leukocyte environment using immunogenetic biomarkers to assess immunocompetence following exposure to weaning stress[J]. BMC Vet Res, 2011, 7: 45.
[25] WANG X, WU H, MILLER A H. Interleukin 1α (IL-1α) induced activation of p38 mitogen-activated protein kinase inhibits glucocorticoid receptor function[J]. Mol Psychiatry, 2004, 9(1): 65-75.
[26] SALEM S, HARRIS T, MOK J S L, et al. Transforming growth factor-β impairs glucocorticoid activity in the A549 lung adenocarcinoma cell line[J]. Br J Pharmacol, 2012, 166(7): 2036-2048.
[27] HU A H, JOSEPHSON M B, DIENER B L, et al. Pro-asthmatic cytokines regulate unliganded and ligand-dependent glucocorticoid receptor signaling in airway smooth muscle[J]. PLoS One, 2013, 8(4): e60452.
[28] KEENAN C R, MOK J S L, HARRIS T, et al. Bronchial epithelial cells are rendered insensitive to glucocorticoid transactivation by transforming growth factor-β1[J]. Respir Res, 2014, 15: 55.
[29] PAN X Y, WANG Y, SU J, et al. The mechanism and significance of synergistic induction of the expression of plasminogen activator inhibitor-1 by glucocorticoid and transforming growth factor beta in human ovarian cancer cells[J]. Mol Cell Endocrinol, 2015, 407: 37-45.
[30] KAM J C, SZEFLER S J, SURS W, et al. Combination IL-2 and IL-4 reduces glucocorticoid receptor-binding affinity and T cell response to glucocorticoids[J]. J Immunol, 1993, 151(7): 3460-3466.
[31] NIMMAGADDA S R, SZEFLER S J, SPAHN J D, et al. Allergen exposure decreases glucocorticoid receptor binding affinity and steroid responsiveness in atopic asthmatics[J]. Am J Respir Crit Care Med, 1997, 155(1): 87-93.
[32] WEBSTER J C, OAKLEY R H, JEWELL C M, et al A. Proinflammatory cytokines regulate human glucocorticoid receptor gene expression and lead to the accumulation of the dominant negative beta isoform: a mechanism for the generation of glucocorticoid resistance[J]. Proc Natl Acad Sci U S A, 2001, 98(12): 6865-6870.
[33] ORII F, ASHIDA T, NOMURA M, et al. Quantitative analysis for human glucocorticoid receptor α/β mRNA in IBD[J]. Biochem Biophys Res Commun, 2002, 296(5): 1286-1294.
[34] STRICKLAND I, KISICH K, HAUK P J, et al. High constitutive glucocorticoid receptor β in human neutrophils enables them to reduce their spontaneous rate of cell death in response to corticosteroids[J]. J Exp Med, 2001, 193(5): 585-594.
[35] WANG Z L, LI P, ZHANG Q H, et al. Interleukin-1β regulates the expression of glucocorticoid receptor isoforms in nasal polyps in vitro via p38 MAPK and JNK signal transduction pathways[J]. J Inflamm, 2015, 12: 3.
[36] SMOAK K A, CIDLOWSKI J A. Mechanisms of glucocorticoid receptor signaling during inflammation[J]. Mech Ageing Dev, 2004, 125(10-11): 697-706.
[37] KINO T, SU Y A, CHROUSOS G P. Human glucocorticoid receptor isoform β: recent understanding of its potential implications in physiology and pathophysiology[J]. Cell Mol Life Sci, 2009, 66(21): 3435-3448.
[38] TORREGO A, PUJOLS L, ROCA-FERRER J, et al. Glucocorticoid receptor isoforms alpha and β in vitro cytokine-induced glucocorticoid insensitivity[J]. Am J Respir Crit Care Med, 2004, 170(4): 420-425.
[39] REICHARDT H M, TUCKERMANN J P, GÖTTLICHER M, et al. Repression of inflammatory responses in the absence of DNA binding by the glucocorticoid receptor[J]. EMBO J, 2001, 20(24): 7168-7173.
[40] TUCKERMANN J P, KLEIMAN A, MORIGGL R, et al. Macrophages and neutrophils are the targets for immune suppression by glucocorticoids in contact allergy[J]. J Clin Invest, 2007, 117(5): 1381-1390.
[41] OGAWA S, LOZACH J, BENNER C, et al. Molecular determinants of crosstalk between nuclear receptors and toll-like receptors[J]. Cell, 2005, 122(5): 707-721.
[42] LYNCH E M, EARLEY B, MCGEE M, et al. Effect of abrupt weaning at housing on leukocyte distribution, functional activity of neutrophils, and acute phase protein response of beef calves[J]. BMC Vet Res, 2010, 6: 39.
[43] LYNCH E M, MCGEE M, DOYLE S, et al. Effect of pre-weaning concentrate supplementation on peripheral distribution of leukocytes, functional activity of neutrophils, acute phase protein and behavioural responses of abruptly weaned and housed beef calves[J]. BMC Vet Res, 2012, 8: 1.
[44] O'LOUGHLIN A, MCGEE M, DOYLE S, et al. Biomarker responses to weaning stress in beef calves[J]. Res Vet Sci, 2014, 97(2): 458-463.
[45] GUPTA S, EARLEY B, CROWE M A. Effect of 12-hour road transportation on physiological, immunological and haematological parameters in bulls housed at different space allowances[J]. Vet J, 2007, 173(3): 605-616.
[46] JONES M L, ALLISON R W. Evaluation of the ruminant complete blood cell count[J]. Vet Clin North Am Food Anim Pract, 2007, 23(3): 377-402.
[47] BORREGAARD N. Neutrophils, from marrow to microbes[J]. Immunity, 2010, 33(5): 657-670.
[48] AMULIC B, CAZALET C, HAYES G L, et al. Neutrophil function: from mechanisms to disease[J]. Annu Rev Immunol, 2012, 30(1): 459-489.
[49] ROSALES C, DEMAUREX N, LOWELL C A, et al. Neutrophils: their role in innate and adaptive immunity[J]. J Immunol Res, 2016, 2016: 1469780.
[50] JAILLON S, GALDIERO M R, PRETE D D, et al. Neutrophils in innate and adaptive immunity[J]. Semin Immunopathol, 2013, 35(4): 377-394.
[51] WEBER P S D, TOELBOELL T, CHANG L C, et al. Mechanisms of glucocorticoid-induced down-regulation of neutrophil L-selectin in cattle: evidence for effects at the gene-expression level and primarily on blood neutrophils[J]. J Leukoc Biol, 2004, 75(5): 815-827.
[52] PITZALIS C, PIPITONE N, PERRETTI M. Regulation of leukocyte-endothelial interactions by glucocorticoids[J]. Ann N Y Acad Sci, 2002, 966: 108-118.
[53] CRONSTEIN B N, KIMMEL S C, LEVIN R I, et al. A mechanism for the antiinflammatory effects of corticosteroids: the glucocorticoid receptor regulates leukocyte adhesion to endothelial cells and expression of endothelial-leukocyte adhesion molecule 1 and intercellular adhesion molecule 1[J]. Proc Natl Acad Sci U S A, 1992, 89(21): 9991-9995.
[54] PITZALIS C, PIPITONE N, BAJOCCHI G, et al. Corticosteroids inhibit lymphocyte binding to endothelium and intercellular adhesion: an additional mechanism for their anti-inflammatory and immunosuppressive effect[J]. J Immunol, 1997, 158(10): 5007-5016.
[55] HEASMAN S J, GILES K M, WARD C, et al. Glucocorticoid-mediated regulation of granulocyte apoptosis and macrophage phagocytosis of apoptotic cells: implications for the resolution of inflammation[J]. J Endocrinol, 2003, 178(1): 29-36.
[56] RODRIGUES-MASCARENHAS S, SANTOS N F D, RUMJANEK V M. Synergistic effect between ouabain and glucocorticoids for the induction of thymic atrophy[J]. Biosci Rep, 2006, 26(2): 159-169.
[57] HICKEY M C, DRENNAN M, EARLEY B. The effect of abrupt weaning of suckler calves on the plasma concentrations of cortisol, catecholamines, leukocytes, acute-phase proteins and in vitro interferon-gamma production[J]. J Anim Sci, 2003, 81(11): 2847-2855.
[58] KIM M H, YANG J Y, UPADHAYA S D, et al. The stress of weaning influences serum levels of acute-phase proteins, iron-binding proteins, inflammatory cytokines, cortisol, and leukocyte subsets in Holstein calves[J]. J Vet Sci, 2011, 12(2): 151-157.
[59] CUPPS T R, EDGAR L C, THOMAS C A, et al. Multiple mechanisms of B cell immunoregulation in man after administration of in vivo corticosteroids[J]. J Immunol, 1984, 132(1): 170-175.
[60] CUPPS T R, GERRARD T L, FALKOFF R J, et al. Effects of in vitro corticosteroids on B cell activation, proliferation, and differentiation[J]. J Clin Invest, 1985, 75(2): 754-761.
[61] MOSMANN T R, COFFMAN R L. TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties[J]. Annu Rev Immunol, 1989, 7(1): 145-173.
[62] PAZIRANDEH A, XUE Y T, PRESTEGAARD T, et al. Effects of altered glucocorticoid sensitivity in the T cell lineage on thymocyte and T cell homeostasis[J]. FASEB J, 2002, 16(7): 727-729.
[63] FRAKER P J, KING L E. Reprogramming of the immune system during zinc deficiency[J]. Annu Rev Nutr, 2004, 24(1): 277-298.
[64] BOMMHARDT U, BEYER M, HÜNIG T, et al. Molecular and cellular mechanisms of T cell development[J]. Cell Mol Life Sci, 2004, 61(3): 263-280.
[65] HEROLD M J, MCPHERSON K G, REICHARDT H M. Glucocorticoids in T cell apoptosis and function[J]. Cell Mol Life Sci, 2006, 63(1): 60-72.
[66] BIOLATTI B, CANNIZZO F T, ZANCANARO G, et al. Effects of low-dose dexamethasone on thymus morphology and immunological parameters in veal calves[J]. J Vet Med A Physiol Pathol Clin Med, 2005, 52(4): 202-208.
[67] CANNIZZO F T, MINISCALCO B, RIONDATO F, et al. Effects of anabolic and therapeutic doses of dexamethasone on thymus morphology and apoptosis in veal calves[J]. Vet Rec, 2008, 163(15): 448-452.
[68] CARROLL J A, ARTHINGTON J D, CHASE C C. Early weaning alters the acute-phase reaction to an endotoxin challenge in beef calves[J]. J Anim Sci, 2009, 87(12): 4167-4172.
[69] FARRAR J D, OUYANG W J, LÖHNING M, et al. An instructive component in T helper cell type 2 (Th2) development mediated by GATA-3[J]. J Exp Med, 2001, 193(5): 643-650.
[70] ROZKOVA D, HORVATH R, BARTUNKOVA J, et al. Glucocorticoids severely impair differentiation and antigen presenting function of dendritic cells despite upregulation of Toll-like receptors[J]. Clin Immunol, 2006, 120(3): 260-271.
[71] HOMMA T, KATO A, HASHIMOTO N, et al. Corticosteroid and cytokines synergistically enhance toll-like receptor 2 expression in respiratory epithelial cells[J]. Am J Respir Cell Mol Biol, 2004, 31(4): 463-469.
[72] DOYLE S L, O’NEILL L A J. Toll-like receptors: from the discovery of NFκB to new insights into transcriptional regulations in innate immunity[J]. Biochem Pharmacol, 2006, 72(9): 1102-1113.
[73] GRIVENNIKOV S I, KUPRASH D V, LIU Z G, et al. Intracellular signals and events activated by cytokines of the tumor necrosis factor superfamily: from simple paradigms to complex mechanisms[J]. Int Rev Cytol, 2006, 252: 129-161.
[74] SCHEINMAN R I, COGSWELL P C, LOFQUIST A K, et al. Role of transcriptional activation of IκBα in mediation of immunosuppression by glucocorticoids[J]. Science, 1995, 270(5234): 283-286.
[75] JU S T, PANKA D J, CUI H L, et al. Fas(CD95)/FasL interactions required for programmed cell death after T-cell activation[J]. Nature, 1995, 373(6513): 444-448.
[76] BRUNNER T, MOGIL R J, LAFACE D, et al. Cell-autonomous Fas (CD95)/Fas-ligand interaction mediates activation-induced apoptosis in T-cell hybridomas[J]. Nature, 1995, 373(6513): 441-444.
[77] DHEIN J, WALCZAK H, BÄUMLER C, et al. Autocrine T-cell suicide mediated by APO-1/(Fas/CD95)[J]. Nature, 1995, 373(6513): 438-441.