Abstract
Objective: Hashimoto’s Thyroiditis (HT) is an autoimmune disease, characterized by chronic inflammation of the thyroid gland with unknown etiologies. Recently, interleukin-33/ST2 (IL- 33/ST2) pathway reveals its participation in the process of several autoimmune diseases. In this study, the role of IL-33/ST2 pathway in the development of HT is investigated.
Methods: The levels of plasma IL-33, sST2 and the frequency of circulating CD4+ST2L+T cells in 30 HT patients and 20 healthy controls were determined by enzyme-linked immunosorbent assay (ELISA) and flow cytometry respectively. The mRNA expressions of related molecules in IL-33/ST2 pathway in thyroid tissues (12 HT patients and 10 controls) were detected by real-time quantitative PCR (RTqPCR). The protein expressions of IL-33 and ST2 were determined by Western blot and immunohistochemistry staining.
Results: The mRNA expressions of plasma IL-33 and sST2 were elevated in HT patients, with an increased ratio of IL-33/sST2. The number of CD4+ST2L+ T cells in PBMCs of HT group was significantly increased when compared to the control group (CON) by Flow cytometry assay. MRNA Expression of IL-33 and ST2 in thyroid tissue and the level of IL-1β and IL-18 were significantly upregulated in HT patients, while IL-5 was down-regulated in HT patients, compared to CON. The expression of IL-1β and IL-18 were positively correlated with the expression of IL-33. Results of western blot and immunohistochemical staining were consistent with qPCR.
Conclusion: IL-33/ST2 pathway participates in HT via affecting the production of inflammatory cytokines.
Keywords: Interleukin-33(IL-33), ST2, hashimoto’s thyroiditis (HT), inflammatory cytokines, soluble ST2, biomarker.
Graphical Abstract
[http://dx.doi.org/10.1016/j.autrev.2014.01.007] [PMID: 24434360]
[http://dx.doi.org/10.1007/s12016-011-8296-5] [PMID: 22231516]
[http://dx.doi.org/10.1016/S0165-2478(99)00156-X] [PMID: 10714432]
[http://dx.doi.org/10.1159/000078438] [PMID: 15249726]
[http://dx.doi.org/10.1016/j.drudis.2015.10.012] [PMID: 26526566]
[http://dx.doi.org/10.3109/08916934.2014.914175] [PMID: 24801540]
[http://dx.doi.org/10.1016/j.imbio.2012.05.016] [PMID: 22878044]
[http://dx.doi.org/10.1016/j.humimm.2012.10.005] [PMID: 23073298]
[http://dx.doi.org/10.1111/j.1365-2613.2010.00715.x] [PMID: 20586818]
[http://dx.doi.org/10.1038/nrd2660] [PMID: 18827826]
[http://dx.doi.org/10.1124/jpet.114.222505] [PMID: 25906776]
[http://dx.doi.org/10.1016/j.humimm.2013.06.029] [PMID: 23800433]
[http://dx.doi.org/10.1007/s10238-010-0115-4] [PMID: 20963466]
[http://dx.doi.org/10.4149/endo_2013_02_57] [PMID: 23641786]
[http://dx.doi.org/10.2332/allergolint.10-RAI-0186] [PMID: 20414050]
[http://dx.doi.org/10.1007/s12026-012-8283-9] [PMID: 22392053]
[http://dx.doi.org/10.1111/imm.12174] [PMID: 24116703]
[http://dx.doi.org/10.1111/j.1365-2249.2012.04629.x] [PMID: 22943195]
[http://dx.doi.org/10.3109/01902148.2013.870261] [PMID: 24446582]
[http://dx.doi.org/10.1002/art.24305] [PMID: 19248109]
[http://dx.doi.org/10.1111/iji.12240] [PMID: 26566691]
[http://dx.doi.org/10.1016/j.jbspin.2011.02.011] [PMID: 21441054]
[http://dx.doi.org/10.1016/j.clim.2011.11.007] [PMID: 22189043]
[http://dx.doi.org/10.1002/eji.201141947] [PMID: 22585447]
[http://dx.doi.org/10.3346/jkms.2011.26.9.1132] [PMID: 21935266]
[http://dx.doi.org/10.1590/S0100-879X2012007500168] [PMID: 23090124]
[http://dx.doi.org/10.1073/pnas.1307321110] [PMID: 23918359]
[http://dx.doi.org/10.1016/j.jaci.2010.11.050] [PMID: 21377040]
[http://dx.doi.org/10.1155/2014/587376] [PMID: 25032216]
[http://dx.doi.org/10.1016/j.cyto.2011.12.010] [PMID: 22239947]
[http://dx.doi.org/10.1093/rheumatology/kep402] [PMID: 20026564]
[http://dx.doi.org/10.1073/pnas.0912678107] [PMID: 20385815]
[http://dx.doi.org/10.1371/journal.pone.0079176] [PMID: 24265755]
[http://dx.doi.org/10.1016/j.yjmcc.2013.03.020] [PMID: 23567618]
[PMID: 26218140]