Advances in Clinical and Experimental Medicine
2018, vol. 27, nr 1, January, p. 99–103
Publication type: original article
Elevated serum concentrations of metalloproteinases (MMP-2, MMP-9) and their inhibitors (TIMP-1, TIMP-2) in patients with Graves’ orbitopathy
1 Department of Hematology, Blood Neoplasms and Bone Marrow Transplantation, Wroclaw Medical University, Poland
2 Department of Ophthalmology, Wroclaw Medical University, Poland
3 Department of Endocrinology, Diabetology and Isotope Treatment, Wroclaw Medical University, Poland
4 Department of Microbiology, Wroclaw Medical University, Poland
5 Department of Cosmetology, Wroclaw Physiotherapy College, Poland
Background. Graves’ orbitopathy (GO), also known as thyroid-associated ophthalmopathy, is characterized by dramatic tissue reactivity. Both inflammation and tissue remodeling characterize the clinical course of GO. Some data has been found regarding the association of MMPs and TIMPs in GO.
Material and Methods. Serum concentrations of MMP-9, MMP-2, TIMP-1, and TIMP-2 were determined by ELISA method.
Objectives. Forty-eight patients (34 females, 14 males, with median age 51.5 years) with GD and hyperthyroidism were enrolled in the study. In 28 patients, active, moderate-to-severe grade orbitopathy was diagnosed. The aim of this study was to assess the serum concentrations of MMP-2, MMP-9, TIMP-1, and TIMP-2 in patients with Graves’ disease (GD), with and without GO, and their relationship with disease severity, as well as to evaluate how these concentrations change after successful treatment.
Results. Median serum concentrations of MMP-2 and MMP-9 were significantly higher in all patients with GD as well as in the subgroup with GO than in the control group. Median serum concentrations of TIMP-1 and TIMP-2 were significantly higher in all patients with GD than in controls. The same significant differences were observed in the subgroups with and without GO in comparison with controls. The GO subgroup showed a significant positive correlation between the MMP-9 concentration and the serum level of TSHRAb antibodies, and a clinical activity score ≥4 according to EUGOGO.
Conclusion. In our study we found that only MMP-9 differentiates the patients with and without GO, and may be used as a marker of the disease severity in patients with this manifestation of GD.
Graves’ disease, matrix metalloproteinases, tissue inhibitors of metalloproteinases, orbithopathy
- Dik WA, Virakul S, van Steensel L. Current perspectives on the role of orbital fibroblasts in the pathogenesis of Graves’ ophthalmopathy. Exp Eye Res. 2016;142:83–91. doi:10.1016/j.exer.2015.02.007.
- Tsai CC, Wu SB, Chang PC, Wei YH. Alteration of connective tissue growth factor (CTGF) expression in orbital fibroblasts from patients with Graves’ ophthalmopathy. PLoS One. 2015;10(11):e0143514.
- Slowik M, Urbaniak-Kujda D, Bohdanowicz-Pawlak A, et al. CD8+CD28-lymphocytes in peripheral blood and serum concentrations of soluble interleukin 6 receptor are increased in patients with Graves’ orbitopathy and correlate with disease activity. Endocr Res. 2012;37(2):89–95. doi:10.3109/07435800.2011.635622.
- Coussens LM, Fingleton B, Matrisian LM. Matrix metalloproteinase inhibitors and cancer: Trials and tribulations. Science. 2002;295(5564):2387–2392.
- Dalberg K, Eriksson E, Enberg U, Kjellman M, Bäckdahl M. Gelatinase A. Membrane type 1 matrix metalloproteinase, and extracellular matrix metalloproteinase inducer mRNA expression: Correlation with invasive growth of breast cancer. World J Surg. 2000;24(3):334–340.
- Liu ZJ, Zhuge Y, Velazquez OC. Trafficking and differentiation of mesenchymal stem cells. J Cell Biochem. 2009;106(6):984–991. doi:10.1002/jcb.22091.
- Lambert E, Dassé E, Haye B, Petitfrère E. TIMPs as multifacial proteins. Crit Rev Oncol Hematol. 2004;49(3):187–198.
- Myśliwiec J, Adamczyk M, Pawłowski P, Nikołajuk A, Górska M. Serum gelatinases (MMP-2 and MMP-9) and VCAM-1 as a guideline in a therapeutic approach in Graves’ ophthalmopathy. Endokrynol Pol. 2007;58(2):105–109.
- Mourits MP, Prummel MF, Wiersinga WM, Koornneef L. Clinical activity score as a guide in the management of patients with Graves’ ophthalmopathy. Clin Endocrinol (Oxf). 1997;47(1):9–14.
- Wiersinga WM, Perros P, Kahaly GJ, et al. Clinical assessment of patients with Graves’ orbitopathy: The European Group on Graves’ Orbitopathy recommendations to generalists, specialists and clinical researchers. European Group on Graves’ Orbitopathy (EUGOGO). Eur J Endocrinol. 2006;155(3):387–389.
- Urbaniak-Kujda D, Kapelko-Slowik K, Prajs I, et al. Increased expression of metalloproteinase-2 and -9 (MMP-2, MMP-9), tissue inhibitor of metalloproteinase-1 and -2 (TIMP-1, TIMP-2), and EMMPRIN (CD147) in multiple myeloma. Hematology. 2016;21(1):26–33.
- Hurnaus S, Mueller-Felber W, Pongratz D, Schoser BG. Serum levels of matrix metalloproteinases-2 and -9 and their tissue inhibitors in inflammatory neuromuscular disorders. Eur Neurol. 2006;55(4):204–208.
- Fiedorczyk M, Klimiuk PA, Sierakowski S, Gindzienska-Sieskiewicz E, Chwiecko J. Serum matrix metalloproteinases and tissue inhibitors of metalloproteinases in patients with early rheumatoid arthritis. J Rheumatol. 2006;33(8):1523–1529.
- Han R, Smith TJ. Induction by IL-1 beta of tissue inhibitor of metalloproteinase-1 in human orbital fibroblasts: Modulation of gene promoter activity by IL-4 and IFN-gamma. J Immunol. 20051;174(5):3072–3079.
- Yoon JS, Chae MK, Lee SY, Lee EJ. Anti-inflammatory effect of quercetin in a whole orbital tissue culture of Graves’ orbitopathy. Br J Ophthalmol. 2012;96(8):1117–1121. doi:10.1136/bjophthalmol-2012–301537.
- Yoon JS, Lee HJ, Choi SH, Chang EJ, Lee SY, Lee EJ. Quercetin inhibits IL-1β-induced inflammation, hyaluronan production and adipogenesis in orbital fibroblasts from Graves’ orbitopathy. PLoS One. 2011;6(10):e26261. doi:10.1371/journal.pone.0026261.
- Yoon JS, Chae MK, Jang SY, Lee SY, Lee EJ. Antifibrotic effects of quercetin in primary orbital fibroblasts and orbital fat tissue cultures of Graves’ orbitopathy. Invest Ophthalmol Vis Sci. 2012;53(9):5921–5929. doi:10.1167/iovs.12–9646.