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Yang Yang, Atsunobu Takeda, Yuji Oshima, Takeru Yoshimura, Koh-hei Sonoda, Tatsuro Ishibashi; Analysis of the Immunomodulatory Roles of Hsp70 in Experimental Subretinal Fibrosis. Invest. Ophthalmol. Vis. Sci. 2012;53(14):4757.
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Subretinal fibrosis often causes destruction of normal retinal structures, including photoreceptor cells, within and/or around the macular area as seen in advanced age-related macular degeneration. Previously we reported that the interactions between active macrophages and retinal pigment epithelial cells (RPEs) play a key role in the development of subretinal fibrosis due to choroidal neovascularization (CNV). Heat shock proteins (HSPs), including HSP70, have recently been shown to act like cytokines to confer cytoprotection in several diseases via Toll-like receptor 2 (TLR2) and TLR4. Here we report the HSP70-induced immunomodulatory property of RPEs in experimental subretinal fibrosis.
Expressions of TLR2 and TLR4 in PEC-inoculated eyes and in HSP70-stimulated cultured RPEs were examined by immunohistochemistry. IL-10 expression by both RPEs and macrophages from WT, TLR2-/- and TLR4-/- mice were assessed by quantitative real-time PCR and ELISA.
Expressions of TLR2 and TLR4 in WT mice after HSP70 administration were detected in the RPE layer around the area where PECs were inoculated. IL-10, known as a potent anti-inflammatory cytokine, was detected in HSP70-stimulated cultured RPEs from WT mice, but not in those from TLR2-/- and TLR4-/- mice. Cultured macrophages from WT mice failed to produce IL-10 in response to HSP70.
RPEs, not macrophages, are the main source of HSP70-mediated IL-10 production via TLR2 and TLR4 signaling pathways. HSP70 may have an important immunomodulatory role in experimental subretinal fibrosis.
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