Responses of Multipotent Retinal Stem Cells to IL-1β, IL-18, or IL-17.
Purpose. To investigate how multipotent retinal stem cells (RSCs) isolated from mice respond to the proinflammatory signaling molecules, IL-1β, IL-18, and IL-17A. Materials and Methods. RSCs were cultured in a specific culture medium and were treated with these cytokines. Cell viability was detected by MTT assay; ultrastructure was evaluated by transmission electron microscopy; expression of IL-17rc and proapoptotic proteins was detected by immunocytochemistry and expression of Il-6 and Il-17a was detected by quantitative RT-PCR. As a comparison, primary mouse retinal pigment epithelium (RPE) cells were also treated with IL-1β, IL-18, or IL-17A and analyzed for the expression of Il-6 and Il-17rc. Results. Treatment with IL-1β, IL-18, or IL-17A decreased RSC viability in a dose-dependent fashion and led to damage in cellular ultrastructure including pyroptotic and/or necroptotic cells. IL-1β and IL-18 could induce proapoptotic protein expression. All treatments induced significantly higher expression of Il-6 and Il-17rc in both cells. However, neither IL-1β nor IL-18 could induce Il-17a expression in RSCs. Conclusions. IL-1β, IL-18, and IL-17A induce retinal cell death via pyroptosis/necroptosis and apoptosis. They also provoke proinflammatory responses in RSCs. Though IL-1β and IL-18 could not induce Il-17a expression in RSCs, they both increase Il-17rc expression, which may mediate the effect of Il-17a.
Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA ; Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China.
Shida
S
Chen
Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Defen
D
Shen
Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Nicholas A
NA
Popp
Histology Core, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Alexander J
AJ
Ogilvy
Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Jingsheng
J
Tuo
Histology Core, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Mones
M
Abu-Asab
Stowers Institute for Medical Research, Kansas City, MO 64110, USA ; Department of Anatomy and Cell Biology, University of Kansas School of Medicine, Kansas City, KS 66160, USA.
Ting
T
Xie
Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Chi-Chao
CC
Chan