Role of the Specialized Pro-resolving Mediator Resolvin D1 in Hashimotoʼs Thyroiditis

Jing Song; Rongxin Sun; Yuanyuan Zhang; Ying Fu; Dong Zhao

doi:10.1055/a-1345-0173

Experimental and Clinical Endocrinology & Diabetes, Table of Contents

Exp Clin Endocrinol Diabetes 2021; 129(11): 791-797
DOI: 10.1055/a-1345-0173

Article

Role of the Specialized Pro-resolving Mediator Resolvin D1 in Hashimotoʼs Thyroiditis

Jing Song

¹Beijing Key Laboratory of Diabetes Research and Care, Center for Endocrine Metabolism and Immune Diseases, Lu He Hospital Capital Medical University, Beijing, China

,

Rongxin Sun

¹Beijing Key Laboratory of Diabetes Research and Care, Center for Endocrine Metabolism and Immune Diseases, Lu He Hospital Capital Medical University, Beijing, China

,

Yuanyuan Zhang

¹Beijing Key Laboratory of Diabetes Research and Care, Center for Endocrine Metabolism and Immune Diseases, Lu He Hospital Capital Medical University, Beijing, China

,

Ying Fu

¹Beijing Key Laboratory of Diabetes Research and Care, Center for Endocrine Metabolism and Immune Diseases, Lu He Hospital Capital Medical University, Beijing, China

,

Dong Zhao

¹Beijing Key Laboratory of Diabetes Research and Care, Center for Endocrine Metabolism and Immune Diseases, Lu He Hospital Capital Medical University, Beijing, China

› Author Affiliations

Abstract

Objective Resolvins are produced by the catabolism of polyunsaturated fatty acids (PUFAs) and play vital roles in inflammation resolution. Resolvins have been associated with autoimmune disorders. This study aimed to measure the level of Resolvin D1 (RVD1) in the serum of Hashimoto's thyroiditis (HT) patients and healthy controls (HCs) and to further analyse its correlation with thyroid autoantibodies and inflammatory factors.

Methods Sixty-three participants were recruited, namely, 30 untreated HT patients and 33 sex- and age-matched HCs. Serum RVD1 and inflammatory chemokine (MCP-1 and IP-10) levels were measured by ELISA according to the manufacturer’s protocol. Serum total T3 (TT3), TT4, free T3 (FT3), FT4, thyroglobulin antibody (TgAb), thyroid peroxidase antibody (TPOAb) and thyroid-stimulating hormone (TSH) levels were measured using an electrochemiluminescence immunoassay. Thyroid homeostasis parameters, including the thyroid secretory capacity (SPINA-GT), the total deiodinase activity (SPINA-GD), Jostel’s TSH index (TSHI) and the thyrotroph thyroid hormone sensitivity index (TTSI), were calculated.

Results Serum RVD1 levels in HT patients (134.76, 85.35–201.36 pg/mL) were significantly lower than those in HCs (187.64, 131.01–326.85 pg/mL) (P=0.004). As the TPOAb level increased, the RVD1 level showed a decreasing trend (P for trend=0.002). Both multinomial and ordinal logistics analyses revealed that serum RVD1 levels were negatively correlated with TPOAb levels in the adjusted models. Moreover, RVD1 showed a negative correlation with the inflammatory chemokine IP-1 0 (r=–0.276, P=0.034), TSHI (r=–0.269, P=0.036) and TTSI (r=–0.277, P=0.031).

Conclusions Thyroid autoimmunity may be associated with low levels of RVD1. Decreased RVD1 levels indicate impaired resolution of inflammation in HT patients.

Key words

Hashimotoʼs thyroiditis - resolvins - serum - TPOAb - thyroid

Full Text

References

References
1 Caturegli P, De Remigis A, Rose NR. Hashimoto thyroiditis: Clinical and diagnostic criteria. Autoimmun Rev 2014; 13: 391-397
2 Hu S, Rayman MP. Multiple Nutritional Factors and the Risk of Hashimotoʼs Thyroiditis. Thyroid 2017; 27: 597-610
3 Rayman MP. Multiple nutritional factors and thyroid disease, with particular reference to autoimmune thyroid disease. Proc Nutr Soc 2019; 78: 34-44
4 Buckley CD, Gilroy DW, Serhan CN. et al. The resolution of inflammation. Nat Rev Immunol 2013; 13: 59-66
5 Korem Kohanim Y, Tendler A, Mayo A. et al. Endocrine autoimmune disease as a fragility of immune surveillance against hypersecreting mutants. Immunity 2020; 52: 872-884 e875
6 Serhan CN, Chiang N, Van Dyke TE. Resolving inflammation: Dual anti-inflammatory and pro-resolution lipid mediators. Nat Rev Immunol 2008; 8: 349-361
7 Basil MC, Levy BD. Specialized pro-resolving mediators: Endogenous regulators of infection and inflammation. Nat Rev Immunol 2016; 16: 51-67
8 Abdolmaleki F, Kovanen PT, Mardani R. et al. Resolvins: Emerging players in autoimmune and inflammatory diseases. Clin Rev Allergy Immunol 2020; 58: 82-91
9 Bannenberg GL, Chiang N, Ariel A. et al. Molecular circuits of resolution: Formation and actions of resolvins and protectins. J Immunol 2005; 174: 4345-4355
10 Ramon S, Gao F, Serhan CN. et al. Specialized proresolving mediators enhance human B cell differentiation to antibody-secreting cells. J Immunol 2012; 189: 1036-1042
11 Chiurchiu V, Leuti A, Dalli J. et al. Proresolving lipid mediators resolvin D1, resolvin D2, and maresin 1 are critical in modulating T cell responses. Sci Transl Med 2016; 8: 353ra111
12 Navarini L, Bisogno T, Margiotta DPE. et al. Role of the Specialized Proresolving Mediator Resolvin D1 in Systemic Lupus Erythematosus: Preliminary Results. J Immunol Res 2018; 2018: 5264195
13 Kooij G, Derada Troletti C, Leuti A. et al. Specialized pro-resolving lipid mediators are differentially altered in peripheral blood of patients with multiple sclerosis and attenuate monocyte and blood-brain barrier dysfunction. Haematologica 2020; 105: 2056-2070
14 Poisson LM, Suhail H, Singh J. et al. Untargeted plasma metabolomics identifies endogenous metabolite with drug-like properties in chronic animal model of multiple sclerosis. J Biol Chem 2015; 290: 30697-30712
15 Sun W, Ma J, Zhao H. et al. Resolvin D1 suppresses pannus formation via decreasing connective tissue growth factor caused by upregulation of miRNA-146a-5p in rheumatoid arthritis. Arthritis Res Ther 2020; 22: 61
16 Gomaa AM, Abd El-Aziz EA. Omega-3 fatty acids decreases oxidative stress, tumor necrosis factor-alpha, and interleukin-1 beta in hyperthyroidism-induced hepatic dysfunction rat model. Pathophysiology 2016; 23: 295-301
17 Benvenga S, Vita R, Di Bari F. et al. Stable consumption of swordfish favors, whereas stable consumption of oily fish protects from, development of postpartum thyroiditis. Endocrine 2019; 65: 94-101
18 Benvenga S, Vigo MT, Metro D. et al. Type of fish consumed and thyroid autoimmunity in pregnancy and postpartum. Endocrine 2016; 52: 120-129
19 Breese McCoy SJ. Coincidence of remission of postpartum Graves' disease and use of omega-3 fatty acid supplements. Thyroid Res 2011; 4: 16
20 Jostel A, Ryder WD, Shalet SM. The use of thyroid function tests in the diagnosis of hypopituitarism: definition and evaluation of the TSH Index. Clin Endocrinol (Oxf) 2009; 71: 529-534
21 Yagi H, Pohlenz J, Hayashi Y. et al. Resistance to thyroid hormone caused by two mutant thyroid hormone receptors beta, R243Q and R243W, with marked impairment of function that cannot be explained by altered in vitro 3,5,3'-triiodothyroinine binding affinity. J Clin Endocrinol Metab 1997; 82: 1608-1614
22 Dietrich JW, Landgrafe-Mende G, Wiora E. et al. Calculated parameters of thyroid homeostasis: Emerging Tools for Differential Diagnosis and Clinical Research. Front Endocrinol (Lausanne) 2016; 7: 57
23 Wang X, Jiao W, Lin M. et al. Resolution of inflammation in neuromyelitis optica spectrum disorders. Mult Scler Relat Disord 2019; 27: 34-41
24 Mitchell S, Thomas G, Harvey K. et al. Lipoxins, aspirin-triggered epi-lipoxins, lipoxin stable analogues, and the resolution of inflammation: stimulation of macrophage phagocytosis of apoptotic neutrophils in vivo. J Am Soc Nephrol 2002; 13: 2497-2507
25 Ruffilli I, Ferrari SM, Colaci M. et al. IP-10 in autoimmune thyroiditis. Horm Metab Res 2014; 46: 597-602
26 Spinosa M, Su G, Salmon MD. et al. Resolvin D1 decreases abdominal aortic aneurysm formation by inhibiting NETosis in a mouse model. J Vasc Surg 2018; 68: 93S-103S
27 Das UN. Lipoxins as biomarkers of lupus and other inflammatory conditions. Lipids Health Dis 2011; 10: 76
28 Das UN. Is There a Role for Bioactive Lipids in the Pathobiology of Diabetes Mellitus?. Front Endocrinol (Lausanne) 2017; 8: 182
29 Luo B, Han F, Xu K. et al. Resolvin D1 programs inflammation resolution by increasing TGF-beta expression induced by dying cell clearance in experimental autoimmune neuritis. J Neurosci 2016; 36: 9590-9603
30 Odusanwo O, Chinthamani S, McCall A. et al. Resolvin D1 prevents TNF-alpha-mediated disruption of salivary epithelial formation. Am J Physiol Cell Physiol 2012; 302: C1331-C1345
31 Easley JT, Maruyama CL, Wang CS. et al. AT-RvD1 combined with DEX is highly effective in treating TNF-alpha-mediated disruption of the salivary gland epithelium. Physiol Rep 2016; 4: e12990
32 Wang CS, Maruyama CL, Easley JT. et al. AT-RvD1 Promotes resolution of inflammation in NOD/ShiLtJ mice. Sci Rep 2017; 7: 45525
33 Anaya JM. Common mechanisms of autoimmune diseases (the autoimmune tautology). Autoimmun Rev 2012; 11: 781-784
34 Schmidt M, Voell M, Rahlff I. et al. Long-term follow-up of antithyroid peroxidase antibodies in patients with chronic autoimmune thyroiditis (Hashimoto's thyroiditis) treated with levothyroxine. Thyroid 2008; 18: 755-760
35 Wichman J, Winther KH, Bonnema SJ. et al. Selenium supplementation significantly reduces thyroid autoantibody levels in patients with chronic autoimmune thyroiditis: A systematic review and meta-analysis. Thyroid 2016; 26: 1681-1692
36 Ruggeri RM, D'Ascola A, Vicchio TM. et al. Selenium exerts protective effects against oxidative stress and cell damage in human thyrocytes and fibroblasts. Endocrine 2020; 68: 151-162
37 Leuti A, Maccarrone M, Chiurchiu V. Proresolving lipid mediators: endogenous modulators of oxidative stress. Oxid Med Cell Longev 2019; 2019: 8107265
38 Saito P, Melo CPB, Martinez RM. et al. The lipid mediator resolvin d1 reduces the skin inflammation and oxidative stress induced by UV irradiation in hairless mice. Front Pharmacol 2018; 9: 1242
39 Chen X, Gong X, Jiang R. et al. Resolvin D1 attenuates CCl4-induced acute liver injury involving up-regulation of HO-1 in mice. Immunopharmacol Immunotoxicol 2016; 38: 61-67
40 Posso SV, Quesnot N, Moraes JA. et al. AT-RVD1 repairs mouse lung after cigarette smoke-induced emphysema via downregulation of oxidative stress by NRF2/KEAP1 pathway. Int Immunopharmacol 2018; 56: 330-338
41 Benabdoune H, Rondon EP, Shi Q. et al. The role of resolvin D1 in the regulation of inflammatory and catabolic mediators in osteoarthritis. Inflamm Res 2016; 65: 635-645
42 Zhang Z, Hu X, Qi X. et al. Resolvin D1 promotes corneal epithelial wound healing and restoration of mechanical sensation in diabetic mice. Mol Vis 2018; 24: 274-285
43 Nie X, Ma X, Xu Y. et al. Increased serum adipocyte fatty acid-binding protein levels are associated with decreased sensitivity to thyroid hormones in the euthyroid population. Thyroid 2020; 30: 1718-1723