December 2016
Volume 57, Issue 15
Open Access
Letters to the Editor  |   December 2016
Author Response: Role of miR-146a in the Regulation of Inflammation in an In Vitro Model of Graves' Orbitopathy
Author Affiliations & Notes
  • Sun Young Jang
    Department of Ophthalmology, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon, Korea; and the
  • Jin Sook Yoon
    Department of Ophthalmology, Severance Hospital, The Institute of Vision Research, Yonsei University College of Medicine, Seoul, Korea.
Investigative Ophthalmology & Visual Science December 2016, Vol.57, 6796. doi:10.1167/iovs.16-20847
  • Views
  • PDF
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to Subscribers Only
      Sign In or Create an Account ×
    • Get Citation

      Sun Young Jang, Jin Sook Yoon; Author Response: Role of miR-146a in the Regulation of Inflammation in an In Vitro Model of Graves' Orbitopathy. Invest. Ophthalmol. Vis. Sci. 2016;57(15):6796. doi: 10.1167/iovs.16-20847.

      Download citation file:


      © 2017 Association for Research in Vision and Ophthalmology.

      ×
  • Supplements
We thank Wang et al.1 for their instructive comments regarding our manuscript entitled, “Role of miR-146a in the Regulation of Inflammation in an In Vitro Model of Graves' Orbitopathy.”2 In our study, we found that the level of miR-146a expression was significantly higher in Graves' orbitopathy (GO) adipose tissue compared with non-GO normal controls. Wang et al.1 questioned the source of the increased miR-146a levels, and cited past reports3,4 that suggested that peripheral blood CD4+ T cells in the orbital adipose tissue may be one of the sources of the increased levels of miR-146a. 
Because microRNA expression is cell- or tissue-specific, we believe further studies are necessary to confirm their hypothesis. In our study, we reported a comparison of the expression levels of miR-146a in GO and non-GO orbital adipose tissues.2 However, we have also obtained data regarding the expression levels of miR-146a in GO and non-GO orbital fibroblasts. This unpublished data showed that the level of miR-146a expression was higher in GO orbital fibroblasts, compared with non-GO fibroblasts. However, the results did not show whether other cell types, such as orbital adipocyte or CD4+T cells, led to increased miR-146a expression in GO patients. To cite one report not consistent with the hypothesis by Wang et al.,1 Liu et al.5 recently reported different miRNA expression in peripheral blood mononuclear cells (PBMCs), consisting of monocytes, T cells, B cells, and other cell types, from 54 Graves' disease (GD) patients and 35 normal controls. The authors reported that changes in levels of miR-154*, miR-374b, and miR-431* were associated with GD, whereas the microarray did not show any significant difference in the miR-146a in PBMCs of GD patients. Although the study did not mention the percentage of GO patients, we believe that some GO patients may have been included in their study. 
In addition, Wang et al.1 suggested a possible role of miR-155 in the regulation of inflammation in GO patients. In previous studies using knockout mice, miR-155 was implicated as a positive regulator of cytokine release from B and T cells.6,7 Then, several recent studies suggested that miR-155 modulates immunity by regulating the Toll-like receptor/IL-1 inflammatory pathway in a similar manner to miR-146.8,9 Ceppi et al.9 reported that miR-155 (and miR-146a) decreased p38 MARK activation and controlled the overproduction of inflammatory cytokines in activated monocyte-derived dendritic cells. 
In humans, miR-155 has been reported to be associated with rheumatoid arthritis (RA),10,11 atherosclerosis,12 and diabetic nephritis (DN).13 Huang et al.13 reported that the expression of both miR-155 and miR-146a increased more than 5-fold in kidney samples of DN patients compared with normal controls. Recently, Li et al.12 reported that an increased miR-155 level relieves chronic inflammation and plays a protective role by signaling through the miR-155-CARHSP1-TNF-α pathway in atherosclerosis. In a similar manner as miR-146a, miR-155 was found to be upregulated in PBMCs,11 as well as in synovial fibroblasts and synovial tissue from RA patients.10 Consistent with these results, most previous studies have reported that both miR-146a and miR-155 were upregulated in inflammatory diseases. We therefore hypothesize that miR-155 plays an important role in the regulation of inflammation in orbital fibroblasts from GO patients, although further studies are needed to confirm the exact role of miR-155 in the regulation of this inflammation. 
We appreciate the comments by Wang, Xiao, and Zhang that prompted us to reevaluate an important point that we had not fully considered. 
Supported by a grant from the National Research Foundation of Korea (2014R1A1002754); and partially supported by the Soonchunhyang University Research Fund. 
References
Wang J, Xiao Y, Zhang H. Role of miR-146a in the regulation of inflammation in an in vitro model of Graves' orbitopathy. Invest Ophthalmol Vis Sci. 2016; 57: 6795.
Jang SY, Chae MK, Lee JH, Lee EJ, Yoon JS. Role of miR-146a in the regulation of inflammation in an in vitro model of Graves' orbitopathy. Invest Ophthalmol Vis Sci. 2016; 57: 4027–4034.
Li J, Wan Y, Guo Q, et al. Altered microRNA expression profile with miR-146a upregulation in CD4+ T cells from patients with rheumatoid arthritis. Arthritis Res Ther. 2010; 12: R81.
Kahaly GJ, Shimony O, Gellman YN, et al. Regulatory T-cells in Graves' orbitopathy: baseline findings and immunomodulation by anti-T lymphocyte globulin. J Clin Endocrinol Metab. 2011; 96: 422–429.
Liu R, Ma X, Xu L, et al. Differential microRNA expression in peripheral blood mononuclear cells from Graves' disease patients. J Clin Endocrinol Metab. 2012; 97: E968–E972.
Rodriguez A, Vigorito E, Clare S, et al. Requirement of bic/microRNA-155 for normal immune function. Science. 2007; 316: 608–611.
Thai TH, Calado DP, Casola S, et al. Regulation of the germinal center response by microRNA-155. Science. 2007; 316: 604–608.
Taganov KD, Boldin MP, Chang KJ, Baltimore D. NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. Proc Natl Acad Sci U S A. 2006; 103: 12481–12486.
Ceppi M, Pereira PM, Dunand-Sauthier I, et al. MicroRNA-155 modulates the interleukin-1 signaling pathway in activated human monocyte-derived dendritic cells. Proc Natl Acad Sci U S A. 2009; 106: 2735–2740.
Stanczyk J, Pedrioli DM, Brentano F, et al. Altered expression of microRNA in synovial fibroblasts and synovial tissue in rheumatoid arthritis. Arthritis Rheum. 2008; 58: 1001–1009.
Pauley KM, Satoh M, Chan AL, Bubb MR, Reeves WH, Chan EK. Upregulated miR-146a expression in peripheral blood mononuclear cells from rheumatoid arthritis patients. Arthritis Res Ther. 2008; 10: R101.
Li X, Kong D, Chen H, et al. miR-155 acts as an anti-inflammatory factor in atherosclerosis-associated foam cell formation by repressing calcium-regulated heat stable protein 1. Sci Rep. 2016; 6: 21789.
Huang Y, Liu Y, Li L, et al. Involvement of inflammation-related miR-155 and miR-146a in diabetic nephropathy: implications for glomerular endothelial injury. BMC Nephrol. 2014; 15: 142.
×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×