SEROLOGICAL AND MOLECULAR EVALUATION OF MRP14 IN THYROIDITIS AND ITS ROLE IN PRO-INFLAMMATORY CHEMOKINES ACTIVATION

Authors

DOI:

https://doi.org/10.36103/ijas.v53i6.1652

Keywords:

S100 A9, autoimmune thyroiditis, hypothyroidism, hyperthyroidism, CXCL9

Abstract

This study was aimed to investigate the involvement of Myeloid Related Protein 14 (MRP14) in the production of CXC Motif Chemokine Ligand 9 (CXCL9) in thyroiditis patients. The first group composed of 27 hypothyroidism (HO) patients (12 men and 15 women), age average about 46 years old. The second group had 43 patients (8 men and 35 women) with hyperthyroidism (HR), their mean of age was 42, while 30 healthy persons act as control group (HC) had an average age of 33.47 of men (13) and women (17). The three groups were testing for triiodothyronine (T3), thyroxine (T4) and thyroid stimulating hormone (TSH) furthermore, testing the thyroglobulin (TG), anti-thyroperoxidase (a-TPO), anti-TSH receptor (TSHR) and serum level of MRP14 by Enzyme-Linked Immunosorbent Assay (ELISA). The results showed a high significant (P< 0.0001) increase in MRP14 levels in hypothyroid group vs hyperthyroidism 123.1 ± 22.39 and 109.8 ± 4.479 ng/ml respectively. MRP14 showed a positive correlation with T4 and a negative correlation with anti-TSHR in HR patients. The gene expression of MRP14 and CXCL9 were assayed to all groups by RT-PCR, results showed a high expression of MRP14 as well as of CXCL9 in the patient groups which showed a high expression of CXCL9 in HO patients. Therefore, the results obtained from the study indicate that the higher concentration of MRP14 expression in Thyroiditis patients might play an important role in the development of the disease mediated by stimulating the secretion of pro-inflammatory chemokines.

References

Al-jumaily, A. K. T., and A. M, Turkie. 2018. Molecular investigation of gene expression of beta-lactamases enzymes gen for Pseudomonas Aeruginosa bacter. The Iraqi Journal of Agricultural Sciences, 49(5), 803

Al-Sa'ady, A. J. R., and M. H, Hilal. 2020. The effect of vitamin d in kidney function and thyroid gland. The Iraqi Journal of Agricultural Sciences, 51(3), 924-929

Alyasin, S.; Karimi, M.; Amin, R.; Babaei, M.; Darougar, S. 2013. Interleukin-17 Gene Expression and Serum Levels in Children with Severe Asthma, Iranian Journal of Immunology, 10 (3):177-185

Antonelli, A., S. M., Ferrari, A., Corrado, A., Di Domenicantonio, and P, Fallahi. 2015. Autoimmune thyroid disorders. Autoimmunity reviews, 14(2), 174-180

Antonelli, A., S. M, Ferrari, D, Giuggioli, E, Ferrannini., C, Ferri., and P, Fallahi. 2014. Chemokine (C–X–C motif) ligand (CXCL) 10 in autoimmune diseases. Autoimmunity reviews, 13(3), 272-280

Antonelli, A., S. M, Ferrari., S, Frascerra., F, Galetta., F, Franzoni., A, Corrado., ... and P, Fallahi. 2011. Circulating chemokine (CXC motif) ligand (CXCL) 9 is increased in aggressive chronic autoimmune thyroiditis, in association with CXCL10. Cytokine, 55(2), 288-293

Antonelli, A., S. M, Ferrari., S, Frascerra., A, Di Domenicantonio., A, Nicolini., P, Ferrari., ... and P, Fallahi. 2011. Increase of circulating CXCL9 and CXCL11 associated with euthyroid or subclinically hypothyroid autoimmune thyroiditis. The Journal of Clinical Endocrinology and Metabolism, 96(6), 1859-1863

Antonelli, A., S. M, Ferrari., P, Fallahi., E, Ghiri., C, Crescioli., P, Romagnani., ... and E, Ferrannini. 2010. Interferon-alpha, -beta and-gamma induce CXCL9 and CXCL10 secretion by human thyrocytes: modulation by peroxisome proliferator-activated receptor-gamma agonists. Cytokine, 50(3), 260-267

Arai, T., C, Kurashima., M, Utsuyama., M, Sawabe., and H, Ito. 2000. Measurement of anti-thyroglobulin and anti-thyroid peroxidase antibodies using highly sensitive radioimmunoassay an effective method for detecting asymptomatic focal lymphocytic thyroiditis in the elderly. Endocrine journal, 47(5), 575-582

Barić, A., L, Brčić., S, Gračan., V, Škrabić., M, Brekalo., M, Šimunac., ... and V, Boraska Perica. 2019. Thyroglobulin antibodies are associated with symptom burden in patients with Hashimoto’s thyroiditis: a cross-sectional study. Immunological investigations, 48(2), 198-209

Begum, A., M. S, Bari., K. F. M, Ayaz., R, Yasmin., N. C, Rajib., M. A, Rashid, and F. M, Siddiqui. 2006. Thyroiditis â A Review. Journal of Medicine, 7(2), 58-63

Bello, F. and A. G, Bakarai. 2012. Hypothyroidism in adults: A review and recent advances in management. Journal of Diabetes and Endocrinology, 3(5):57-69

Burek, C. L., and M. V, Talor. 2009. Environmental triggers of autoimmune thyroiditis. Journal of Autoimmunity, 33(3-4), 183-189

Cengiz, H., T, Demirci., C, Varim., and E, Gönüllü. 2021. The relationship between serum calprotectin levels and disease activity in patients with subacute thyroiditis. European Review for Medical and Pharmacological Sciences, 25(10), 3745-3751

Chaker, L., A. C, Bianco., J, Jonklaas and R. P, Peeters. 2017 Hypothyroidism. Lancet, doi:10.1016/s0140-6736(17)30703-1

Chernov, A. V., J, Dolkas., K, Hoang., M, Angert., G, Srikrishna., T, Vogl., S, Baranovskaya., A.Y, Strongin and V.I, Shubayev. 2015. The calciumbinding proteins S100a8 and S100a9 initiate the early inflammatory program in injured peripheral nerves. J. Biol. Chem. 290: 11771–11784

Dumont, J., R, Opitz., D, Christophe., G, Vassart., P. P, Roger., and C, Maenhaut. 2011. Ontogeny, anatomy, metabolism and physiology of the thyroid. Thyroid Dis. Manag, 1-102

El Gazzar, M. 2015. Immunobiology of S100A8 and S100A9 proteins and their role in acute inflammation and sepsis. Int J Immunol Immunother, 2(2).

Elia, G., and G, Guglielmi. 2018. CXCL9 chemokine in ulcerative colitis. La Clinica Terapeutica, 169(5), e235-e241

Fadhil, M. F., S. R, Ibraheem., and A. A. K. A, Al-Kazaz. 2019. Study the association between IL-17 level and autoimmune antibodies in hypo and hyper thyroidisms patients. Iraqi Journal of Science, 1967-1976

Figueroa Vega, N.; M, Alfonso Pérez.; I, Benedicto.; F, Sánchez Madrid.; R, González Amaro and M, Marazuela. 2010. Increased circulating pro inflammatory cytokines and Th17 lymphocytes in Hashimoto’s thyroiditis. J Clin Endocrinol Metab, 95:953-62

Fritz, G., H. M, Botelho., L. A, Morozova‐Roche., and C. M, Gomes 2010. Natural and amyloid self‐assembly of S100 proteins: structural basis of functional diversity. The FEBS Journal, 277(22), 4578-4590

Hasan, R. I., and A. H, Raziq 2019. Studying the frequency of autoimmune thyroid diseases in duhok province. Science Journal of University of Zakho, 7(2), 45-49

Holzinger, D., D, Foell., and C, Kessel 2018. The role of S100 proteins in the pathogenesis and monitoring of autoinflammatory diseases. Molecular and cellular pediatrics, 5(1), 1-5

Kahaly, G. J., T, Diana., and P. D, Olivo 2020. TSH receptor antibodies: relevance and utility. Endocrine Practice, 26(1), 97-106

Kahaly, G. J. and T, Diana 2017. TSH receptor antibody functionality and nomenclature. Front Endocrinol (Lausanne), 8:28

Kim, J. W., J, Ko., J, Kim., and J. S, Yoon 2020. Proinflammatory effects of calprotectin in Graves’ orbitopathy. Ocular Immunology and Inflammation, 28(1), 156-163

Korkmaz, H., S, Tabur., E, Savaş., M, Özkaya., N, Aksoy., Ş. N, Aksoy., and E, Akarsu 2016. Evaluation of serum S100A8/S100A9 levels in patients with autoimmune thyroid diseases. Balkan Medical Journal, 33(5), 547-551

Lindberg, B., J, Svensson., U. B, Ericsson., P, Nilsson., E, Svenonius., and S. A, Ivarsson 2001. Comparison of some different methods for analysis of thyroid autoantibodies: importance of thyroglobulin autoantibodies. Thyroid, 11(3), 265-269

Luo, X., T, Zheng., C, Mao., X, Dong., X, Mou., C, Xu., ... and Y, Xiao. 2018. Aberrant MRP14 expression in thyroid follicular cells mediates chemokine secretion through the IL-1β/MAPK pathway in Hashimoto’s thyroiditis. Endocrine Connections, 7(6), 850-858

Nacken, W., J, Roth., C, Sorg., and C, Kerkhoff 2003. S100A9/S100A8: Myeloid representatives of the S100 protein family as prominent players in innate immunity. Microscopy research and technique, 60(6), 569-580

Peng, S., X, Sun., X, Wang., H, Wang., Z, Shan., W, Teng., and C, Li 2018. Myeloid related proteins are up-regulated in Autoimmune Thyroid Diseases and activate toll-like receptor 4 and pro-inflammatory cytokines in vitro. International immunopharmacology, 59, 217-226

Pezzano, M. 2019. MIG in autoimmune thyroiditis: review of the literature. La Clinica Terapeutica, 170(4), e295-e300

Ross, D. S., H. B, Burch., D. S, Cooper., M. C, Greenlee., P, Laurberg., A. L, Maia., ... and M. A, Walter 2016. 2016 American Thyroid Association guidelines for diagnosis and management of hyperthyroidism and other causes of thyrotoxicosis. Thyroid, 26(10), 1343-1421

Schäfer, B. W., and C. W, Heizmann 1996. The S100 family of EF-hand calcium-binding proteins: functions and pathology. Trends in biochemical sciences, 21(4), 134-140

Schmittgen, T. D., and K. J, Livak. 2008. Analyzing real-time PCR data by the comparative CT method. Nature Protocols, 3(6), 1101-1108

Stroncek, D. F., R. A, Shankar., and K. M, Skubitz. 2005. The subcellular distribution of myeloid-related protein 8 (MRP8) and MRP14 in human neutrophils. Journal of Translational Medicine, 3(1), 1-9

Touma, M. M., H. S, Jassim., S. M, Hyyawi., H. J, Nayyef., and A. H, Abbas. 2021. The role of ifn-γ and tnf-α in experimental mastitis. The Iraqi Journal of Agricultural Sciences, 52(1):121-128

Vogl, T., K, Tenbrock., S, Ludwig., N, Leukert., C, Ehrhardt., M. A, Van Zoelen., and J, Roth. 2007. Mrp8 and Mrp14 are endogenous activators of Toll-like receptor 4, promoting lethal, endotoxin-induced shock. Nature Medicine, 13(9), 1042-1049

Wu, Z., Y, Zhu., M, Zhang., C, Wang., L, Zhou., W, Liu., ... and L, Ji. 2021. Serum ratio of free triiodothyronine to thyroid-stimulating hormone: a novel index for distinguishing graves’ disease from autoimmune thyroiditis. Frontiers in Endocrinology, 11, 1087

Yan, W. X., C, Armishaw., J, Goyette., Z, Yang., H, Cai., P, Alewood., and C. L, Geczy. 2008. Mast cell and monocyte recruitment by S100A12 and its hinge domain. Journal of Biological Chemistry, 283(19), 13035-13043

Zhai, X., L, Zhang., L, Chen., X, Lian., C, Liu., B, Shi., ... and W, Teng. 2018. An age-specific serum thyrotropin reference range for the diagnosis of thyroid diseases in older adults: a cross-sectional survey in China. Thyroid, 28(12), 1571-1579

Zheng, T., C, Xu., C, Mao., X, Mou., F, Wu., X, Wang., ... and Y, Xiao. 2018. Increased interleukin-23 in Hashimoto’s thyroiditis disease induces autophagy suppression and reactive oxygen species accumulation. Frontiers in immunology, 9, 96.

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Published

2022-12-29

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How to Cite

Hussein, A. M., & Al Sahlanee, R. (2022). SEROLOGICAL AND MOLECULAR EVALUATION OF MRP14 IN THYROIDITIS AND ITS ROLE IN PRO-INFLAMMATORY CHEMOKINES ACTIVATION . IRAQI JOURNAL OF AGRICULTURAL SCIENCES, 53(6), 1368-1376. https://doi.org/10.36103/ijas.v53i6.1652

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