Retinal Astrocytes respond to IL-17 differently than Retinal Pigment Epithelial cells.
IL-17+ T cells make up the majority of the infiltrating cells in the inflamed eye during the development of EAU. However, the role of IL-17 in ocular inflammation is poorly defined. Given that the primary target cells for IL-17 are parenchymal cells of the tissue, we investigated the in vitro effect of IL-17 on mouse RACs and RPE cells. Our results showed that although RACs and RPE cells expressed the IL-17R, RACs responded to IL-17 by producing increased amounts of proinflammatory cytokines and chemokines, leading to increased migration of granulocytes, whereas RPE cells responded to the same concentration of IL-17 by expressing increased levels of SOCS proteins, resulting in only limited production of proinflammatory cytokines and chemokines and an increased amount of suppressive cytokines, such as LIF. The combination of IL-17 and IFN-gamma had a synergistic effect on cell migration with RACs but an antagonistic effect with RPE. In addition, specific inhibitors of the PI3K/Akt signaling pathway completely blocked inflammatory cell migration induced by chemokines released by IL-17-stimulated RACs. Our results demonstrate that IL-17 can induce a pro- or anti-inflammatory effect in the eye, depending on the parenchymal cells stimulated.
Ke
Yan
Y
Department of Ophthalmology and Visual Sciences, Kentucky Lions Eye Center, University of Louisville, Louisville, Kentucky 40202, USA.
Jiang
Guomin
G
Sun
Deming
D
Kaplan
Henry J
HJ
Shao
Hui
H
D000818:Animals; D000998:Antiviral Agents / Q000276:immunology / Q000494:pharmacology; D001253:Astrocytes / Q000166:cytology / Q000276:immunology*; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology*; D018925:Chemokines / Q000276:immunology; D004847:Epithelial Cells / Q000166:cytology / Q000276:immunology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology*; D007249:Inflammation / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology / Q000494:pharmacology; D020381:Interleukin-17 / Q000276:immunology* / Q000494:pharmacology; D051379:Mice; D009928:Organ Specificity / Q000187:drug effects / Q000276:immunology; D019869:Phosphatidylinositol 3-Kinases / Q000276:immunology; D051057:Proto-Oncogene Proteins c-akt / Q000276:immunology; D055213:Retinal Pigment Epithelium / Q000166:cytology / Q000276:immunology*; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D050826:Suppressor of Cytokine Signaling Proteins / Q000276:immunology
D000998:Antiviral Agents; D018925:Chemokines; D020381:Interleukin-17; D050826:Suppressor of Cytokine Signaling Proteins; D007371:Interferon-gamma; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt
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