ADRENAL GLAND TLR EXPRESSION IN ApoE DEFICIENT HOMOZYGOUS (ApoE KO-/-) MICE WITH IMPAIRED THYROID FUNCTION
Abstract
The main aim of our study was to investigate the expression of TLR receptors in the adrenal gland of ApoE knockout mice in context of ApoE deficiency as well as impaired thyroid function (hypo- and hyperthyroidism). The study was conducted on two following experimental animal groups: hypothyroid homozygous mice (ApoE KO-/-) treated with PTU; hyperthyroid homozygous mice (ApoE KO-/-) treated with L-thyroxine (T4) and two control groups: euthyroid homozygous mice (ApoE KO-/-) and euthyroid wild-type C57BL/6 mice (Bb). Determination of TLR gene expression in the adrenal gland was performed by RT-PCR reaction with semi-quantitative detection of populations of mRNA molecules transcribed from the TLR2, TLR4 and TLR9 genes in the adrenal gland in the treated experimental groups and the two untreated control groups. The results of our study are in support of the hypothesis that both conditions of impaired thyroid function produce TLR agonists that increase the expression of TLR in the adrenal gland (p<0,05). Also, in the untreated/control group of mice (ApoE KO-/-), an increased expression of TLR was found compared to the wild strain C57BL/6 mice (Bb) as a control group (p<0.001).
Keywords: TLR receptors, adrenal gland, ApoE deficiency, Hypothyroid, Hyperthyroid.
References
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34.Konstantinidis K, Kitsis RN. Cardiovascular biology: Escaped DNA inflames the heart. Nature 2012; 485(7397):179-80
35.Okabe Y, Kawane K, Akira S, Taniguchi T, Nagata S. Toll-like receptor-independent gene induction program activated by mammalian DNA escaped from apoptotic DNA degradation. J Exp Med. 2005; 21;202(10):1333-9. doi: 10.1084/jem.20051654. PMID: 16301743; PMCID: PMC2212973.
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38.Johnson EO, Calogero AE, Konstandi M, Kamilaris TC, La Vignera S, Chrousos GP. Effects of short- and long-duration hypothyroidism on hypothalamic-pituitary-adrenal axis function in rats: in vitro and in situ studies. Endocrin. 2012; 42(3):684-93
39.Johnson EO, Kamilaris TC, Calogero AE, Gold PW, Chrousos GP. Experimentally-induced hyperthyroidism is associated with activation of the rat hypothalamic-pituitary-adrenal axis. Eur J Endocrinol. 2005; 153(1):177-85.
40.Bornstein SR, Zacharowski P, Schumann RR, Barthel A, Tran N, Papewalis C, Rettori V, McCann SM, Schulze-Osthoff K, Scherbaum WA, Tarnow J, Zacharowski K. Impaired adrenal stress response in Toll-like receptor 2-deficient mice. Proc Natl Acad Sci USA 2004b.; 101: 16695-16700
41.Cheng W, Lau OD, Abumrad NA. Two antiatherogenic effects of progesterone on human macrophages; inhibition of cholesteryl ester synthesis and block of its enhancement by glucocorticoids. J Clin Endocrinol Metab. 1999; 84: 265–271
42.Penfornis P, Viengchareun S, Le Menuet D, Cluzeaud F, Zennaro MC, Lombes M. The mineralocorticoid receptor mediates aldosterone-induced differentiation of T37i cells into brown adipocytes. Am J Physiol Endocrinol Metab. 2000; 279: E386–E394
43.Feingold KR, Shigenaga JK, Kazemi MR, McDonald CM, Patzek SM, Cross AS, Moser A, Grunfeld C. Mechanisms of triglyceride accumulation in activated macrophages. J. Leukoc. Biol. 2012; 92:829-839
44.Boord JB, Fazio S, Linton MF. Cytoplasmic fatty acid-binding proteins: emerging roles in metabolism and atherosclerosis. Curr Opin Lipidol. 2002; 13(2):141-147
45.Storch J, Thumser AE. Tissue-specific functions in the fatty acid-binding protein family. J Biol Chem. 2010; 285(43):32679-32683.
46.Peeters W, de Kleijn DP, Vink A, van de Weg S, Schoneveld AH, Sze SK, van der Spek PJ, de Vries JP, Moll FL, Pasterkamp G. Adipocyte fatty acid binding protein in atherosclerotic plaques is associated with local vulnerability and is predictive for the occurrence of adverse cardiovascular events. Eur Heart J. 2011; 32(14):1758-1768
47.Saruta Т. Mechanism of Glucocorticoid -Induced Hypertension. Hypertens Res. 1996; 19:1-8
48.Ong SLH and Whitworth JA. Glucocorticoid-induced hypertension and the nitric oxide system. Expert Review of Endocrinology & Metabolism 2012; 7(3):273-280.
2.Michelsen KS, Wong MH, Shah PK, Zhang W, Yano J, Doherty TM, Akira S, Rajavashisth TB, Arditi M. Lack of Toll-like receptor 4 or myeloid differentiation factor 88 reduces atherosclerosis and alters plaque phenotype in mice deficient in apolipoprotein E. Proc Natl Acad Sci U S A 2004; 101(29): 10679-84
3.Tran N et all. () Toll-Like Receptor 9 Expression in Murine and Human Adrenal Glands and Possible Implications during Inflammation. The Journal of Clinical Endocrinology & Metabolism 2007; 92(7):2773–2783
4.Kazemi MR, McDonald CM, Shigenaga JK, Grunfeld C, Feingold KR. Adipocyte fatty acid-binding protein expression and lipid accumulation are increased during activation of murine macrophages by toll-like receptor agonists. Arterioscler Thromb Vasc Biol. 2005; 25(6): 1220-1224
5.Miller YI, Viriyakosol S, Worrall DS, Boullier A, Butler S, Witztum JL. Toll-Like Receptor 4–Dependent and –Independent Cytokine Secretion Induced by Minimally Oxidized Low-Density Lipoprotein in Macrophages. Arterioscler Thromb Vasc Biol. 2005; 25: 1213-1219.
6.Erridge C. Endogenous ligands of TLR2 and TLR4: agonists or assistants? Journal of Leukocyte Biologyvol. 2010; 87(6): 989-999
7.Watts GF and Chan DC. Of Mice and Men: Blowing Away the Cobwebs From the Mechanism of Action of Niacin on HDL Metabolism. Arterioscler Thromb Vasc Biol. 2008; 28:1892-1895
8.Ferreira E, Silva AE, Serakides R, Gomes AES, Cassali GD. Model of induction of thyroid dysfunctions in adult female mice. Arq Bras Med Vet Zootec. 2007; 59(5): 1245-49
9.Mysliwiec J et all. Role of interleukin-6 on RANKL-RANK/osteoprotegerin system in hypothyroid ovariectomized mice. Folia Histochem Cytobiol. 2010; 48(4):549-54
10.Tamaru M et all. Dendritic cells produce interleukin-12 in hyperthyroid mice. European Journal of Endocrinology 1999; 141: 625–629
11.Weibel, E.R. Stereological methods. Practical methods for biological morphometry. Academic Press, London. 1979
12.Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987; 162(1):156-9.
13.Applequist SE, Wallin RPA, Ljunggren HG.Variable expression of Toll-like receptor in murine innate and adaptive immune cell lines. Int Immunol. 2002; 14:1065-1074
14.Frantz S, Kelly RA, Bourcier T. Role of TLR-2 in the activation of nuclear factor kappaB by oxidative stress in cardiac myocytes. J Biol Chem. 2001; 276(7):5197-203
15.Paul-Clark MJ, McMaster SK, Sorrentino R, Sriskandan S, Bailey LK, Moreno L, Ryffel B, Quesniaux VF, Mitchell JA. Toll-like receptor 2 is essential for the sensing of oxidants during inflammation. Am J Respir Crit Care Med. 2009; 179(4):299-306
16.Wang XY, Sarkar D, Fisher PB. Stress-sensing toll-like receptor as a driver of angiogenesis. Pigment Cell Melanoma Res. 2011; 24(1):7-9
17.Malinin NL, West XZ, Byzova TV. Oxidation as "the stress of life". Aging (Albany NY) 2011; 3(9):906-10.
18.Sánchez E, Orozco G, and J. MartÃn J. Toll-like receptors and human pathology. InmunologÃa 2004; 23(4): 328-338.
19.Tsan MF, Gao B. Endogenous ligands of Toll-like receptors. J Leukoc Biol. 2004; 76(3):514-9
20.Bornstein SR, Schumann RR, Rettori V, McCann SM, Zacharowski K. Toll-like receptor 2 and Toll-like receptor 4 expression in human adrenals. Horm Metab Res. 2004a.; 36: 470–473.
21.Vakharia K and Hinson JP. () Lipopolysaccharide Directly Stimulates Cortisol Secretion by Human Adrenal Cells by a Cyclooxygenase-Dependent Mechanism. Endocrinology 2005; 146(3):1398–1402
22.Miyata M. and Smith JD.Ðpolipoprotein E allele-specific antioxidant activity and effects on cytotoxicity by oxidative insults and β-amyloid peptides. Nat. Genet.1996; 14: 55-61
23.Stannard AK, Riddell DR, Sacre SM, Tagalakis AD, Langer C, von Eckardstein A, Cullen P, Athanasopoulo T, Dickson G and Owen JS. Cell-derived apolipoprotein E (ApoE) particles Inhibit vascular cell adhesion molecule-1 (VCAM-1) expression in human endothelial cells. J. Biol. Chem. 2001; 276: 46011-46016
24.Ishigami M, Swertfege, DK, Hui MS, Granholm NA and Hui DY. Apolipoprotein E inhibition of vascular smooth muscle cell proliferation but not the inhibition of migration is mediated through activation of inducible nitric oxide synthase. Arterioscler. Thromb. Vasc. Biol. 2000; 20: 1020-1026
25.Kawamura A, Baitsch D, Telgmann R, Feuerborn R, Weissen-Plenz G, Hagedorn C, Saku K, Brand-Herrmann SM, von Eckardstein A, Assmann G and Nofer JR. Apolipoprotein E interrupts interleukin-1β signaling in vascular smooth muscle cells. Arterioscler. Thromb. Vasc. Biol. 2007; 27: 1610-1617
26.Zhu Y, Kodvawala A, Hui DY. Apolipoprotein E inhibits toll-like receptor (TLR)-3- and TLR-4-mediated macrophage activation through distinct mechanisms. Biochem J. 2010; 428(1): 47-54
27.Vedhachalam C, Narayanaswami V, Neto N, Forte TM, Phillips MC, Lund-Katz S and Bielicki JK. The C-terminal lipid-binding domain of apolipoprotein E is a highly efficient mediator of ABCA1-dependent cholesterol efflux that promotes the assembly of high-density lipoproteins. Biochemistry 2007; 46: 2583-2593
28.Riis AL, Gravholt CH, Djurhuus CB, Norrelund H, Jprgensen JO, Moller N. Elevated regional lipolysis in hyperthyroidism. J Clin Endocrinol Metab. 2002: 87: 4747-4753
29.Shi H, Kokoeva MV, Inouye K, Tzameli I, Yin H, Flier JS. TLR4 links innate immunity and fatty acid-induced insulin resistance. J Clin Invest. 2006; 116(11):3015-25.
30.Kim F, Pham M, Luttrell I, Bannerman DD, Tupper J, Thaler J, Hawn TR, Raines EW, Schwartz MW. Toll-like receptor-4 mediates vascular inflammation and insulin resistance in diet-induced obesity. Circ Res. 2007; 100(11):1589-96
31.Brenta G. Why Can Insulin Resistance Be a Natural Consequence of Thyroid Dysfunction? J Thyroid Res. 2011; 2011:152850.
32.Costantini F, Pierdomenico SD, De Cesare D, De Remigis P, Bucciarelli T, Bittolo-Bon G, Cazzolato G, Nubile G, Guagnano MT, Sensi S, Cuccurullo F, Mezzetti A. Effect of thyroid function on LDL oxidation. Arterioscler Thromb Vasc Biol. 1998;18(5):732-7.
33.Geng H, Wang A, Rong G, Zhu B, Deng Y, Chen J, Zhong R. The effects of ox-LDL in human atherosclerosis may be mediated in part via the toll-like receptor 4 pathway. Mol Cell Biochem. 2010 Sep;342(1-2):201-6. doi: 10.1007/s11010-010-0484-8. Epub 2010 May 14. PMID: 20467793.
34.Konstantinidis K, Kitsis RN. Cardiovascular biology: Escaped DNA inflames the heart. Nature 2012; 485(7397):179-80
35.Okabe Y, Kawane K, Akira S, Taniguchi T, Nagata S. Toll-like receptor-independent gene induction program activated by mammalian DNA escaped from apoptotic DNA degradation. J Exp Med. 2005; 21;202(10):1333-9. doi: 10.1084/jem.20051654. PMID: 16301743; PMCID: PMC2212973.
36.Ding Z, Liu S, Wang X, Khaidakov M, Dai Y, Mehta JL. Oxidant stress in mitochondrial DNA damage, autophagy and inflammation in atherosclerosis. Sci Rep. 2013; 3:1077. doi:10.1038/ srep 0107
37.Oka T, Hikoso S, Yamaguchi O, Taneike M, Takeda T, Tamai T, Oyabu J, Murakawa T, Nakayama H, Nishida K, Akira S, Yamamoto A, Komuro I, Otsu K. Mitochondrial DNA that escapes from autophagy causes inflammation and heart failure. Nature 2012; 485(7397):251-255
38.Johnson EO, Calogero AE, Konstandi M, Kamilaris TC, La Vignera S, Chrousos GP. Effects of short- and long-duration hypothyroidism on hypothalamic-pituitary-adrenal axis function in rats: in vitro and in situ studies. Endocrin. 2012; 42(3):684-93
39.Johnson EO, Kamilaris TC, Calogero AE, Gold PW, Chrousos GP. Experimentally-induced hyperthyroidism is associated with activation of the rat hypothalamic-pituitary-adrenal axis. Eur J Endocrinol. 2005; 153(1):177-85.
40.Bornstein SR, Zacharowski P, Schumann RR, Barthel A, Tran N, Papewalis C, Rettori V, McCann SM, Schulze-Osthoff K, Scherbaum WA, Tarnow J, Zacharowski K. Impaired adrenal stress response in Toll-like receptor 2-deficient mice. Proc Natl Acad Sci USA 2004b.; 101: 16695-16700
41.Cheng W, Lau OD, Abumrad NA. Two antiatherogenic effects of progesterone on human macrophages; inhibition of cholesteryl ester synthesis and block of its enhancement by glucocorticoids. J Clin Endocrinol Metab. 1999; 84: 265–271
42.Penfornis P, Viengchareun S, Le Menuet D, Cluzeaud F, Zennaro MC, Lombes M. The mineralocorticoid receptor mediates aldosterone-induced differentiation of T37i cells into brown adipocytes. Am J Physiol Endocrinol Metab. 2000; 279: E386–E394
43.Feingold KR, Shigenaga JK, Kazemi MR, McDonald CM, Patzek SM, Cross AS, Moser A, Grunfeld C. Mechanisms of triglyceride accumulation in activated macrophages. J. Leukoc. Biol. 2012; 92:829-839
44.Boord JB, Fazio S, Linton MF. Cytoplasmic fatty acid-binding proteins: emerging roles in metabolism and atherosclerosis. Curr Opin Lipidol. 2002; 13(2):141-147
45.Storch J, Thumser AE. Tissue-specific functions in the fatty acid-binding protein family. J Biol Chem. 2010; 285(43):32679-32683.
46.Peeters W, de Kleijn DP, Vink A, van de Weg S, Schoneveld AH, Sze SK, van der Spek PJ, de Vries JP, Moll FL, Pasterkamp G. Adipocyte fatty acid binding protein in atherosclerotic plaques is associated with local vulnerability and is predictive for the occurrence of adverse cardiovascular events. Eur Heart J. 2011; 32(14):1758-1768
47.Saruta Т. Mechanism of Glucocorticoid -Induced Hypertension. Hypertens Res. 1996; 19:1-8
48.Ong SLH and Whitworth JA. Glucocorticoid-induced hypertension and the nitric oxide system. Expert Review of Endocrinology & Metabolism 2012; 7(3):273-280.
Published
2023-12-27
How to Cite
TRIPUNOSKI, Toni et al.
ADRENAL GLAND TLR EXPRESSION IN ApoE DEFICIENT HOMOZYGOUS (ApoE KO-/-) MICE WITH IMPAIRED THYROID FUNCTION.
Journal of Morphological Sciences, [S.l.], v. 6, n. 3, p. 99-108, dec. 2023.
ISSN 2545-4706.
Available at: <https://jms.mk/jms/article/view/vol6no3-13>. Date accessed: 22 oct. 2024.
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