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IL-10 is significantly involved in HSP70-regulation of experimental subretinal fibrosis.

ABSTRACT: Subretinal fibrosis is directly related to severe visual loss, especially if occurs in the macula, and is frequently observed in advanced age-related macular degeneration and other refractory eye disorders such as diabetic retinopathy and uveitis. In this study, we analyzed the immunosuppressive mechanism of subretinal fibrosis using the novel animal model recently demonstrated. Both TLR2 and TLR4 deficient mice showed significant enlargement of subretinal fibrotic area as compared with wild-type mice. A single intraocular administration of heat shock protein 70 (HSP70), which is an endogenous ligand for TLR2 and TLR4, inhibited subretinal fibrosis in wild-type mice but not in TLR2 and TLR4-deficient mice. Additionally, HSP70 induced IL-10 production in eyes from wild-type mice but was impaired in both TLR2- and TLR4-deficient mice, indicating that HSP70-TLR2/TLR4 axis plays an immunomodulatory role in subretinal fibrosis. Thus, these results suggest that HSP70-TLR2/TLR4 axis is a new therapeutic target for subretinal fibrosis due to prognostic CNV.

SUBMITTER: Yang Y

PROVIDER: S-EPMC3869650 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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IL-10 is significantly involved in HSP70-regulation of experimental subretinal fibrosis.

Yang Yang Y Takeda Atsunobu A Yoshimura Takeru T Oshima Yuji Y Sonoda Koh-Hei KH Ishibashi Tatsuro T

PloS one 20131220 12

Subretinal fibrosis is directly related to severe visual loss, especially if occurs in the macula, and is frequently observed in advanced age-related macular degeneration and other refractory eye disorders such as diabetic retinopathy and uveitis. In this study, we analyzed the immunosuppressive mechanism of subretinal fibrosis using the novel animal model recently demonstrated. Both TLR2 and TLR4 deficient mice showed significant enlargement of subretinal fibrotic area as compared with wild-typ ...[more]

PMID: 24376495

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Project description:Surgeries, particularly ileocecal resection (ICR), are often required in the treatment of Crohn's disease (CD). However, recurrences are common for patients who undergo ICR, and anastomotic fibrosis is the main cause of re-operation. The present study aimed to investigate the therapeutic effects of triptolide (TPL) in ameliorating fibrosis following ileocolonic anastomosis. A model of IL‑10‑/‑ mice undergoing ICR was used to study postsurgical inflammation and fibrosis of anastomosis. For this purpsose, interleukin (IL)‑10‑/‑ mice were randomly divided into 3 groups as follows: the control group, the saline‑treated group subjected to ICR (ST‑ICR) and the TPL‑treated group subjected to ICR (TT‑ICR). Wild‑type (WT) mice of matching ages were assigned to the WT group. The effects of TPL treatment on ileocolonic anastomosis were determined by histopathological evaluation, western blot analysis and ELISA. The analysis of the effects of TPL treatment on microRNA‑16‑1 (miR‑16‑1) and heat shock protein 70 (HSP70) expression was carried out by RT‑qPCR and western blot analysis. Compared with the control group, significantly higher inflammation scores following anastomosis were observed in the ST‑ICR group (P<0.05), although reversion was observed in the TT‑ICR group, which was consistent with changes in the area of CD4+ cell infiltration. The elevated fibrosis scores and the overexpression of procollagen I and III in the ST‑ICR group were all inhibited by TPL. With an increase in the severity of inflammation and fibrosis, the levels of IL‑6, tumor necrosis factor‑α (TNF‑α) and transforming growth factor‑β1 (TGF‑β1) increased; however, a significant decrease in these levels was observed following treatment with TPL (P<0.05). The results of RT‑qPCR revealed that the upregulated miR‑16‑1 levels in the ST‑ICR group were significantly reduced by TPL. HSP70, which can be inhibited by miR-16-1, ameliorates anastomotic inflammation and fibrosis. Thus, the present study demonstrates that TPL exerts a protective effect against fibrosis following anastomosis in CD. The miR‑16‑1/HSP70 signaling pathway, which can be regulated by TPL, may thus represent a novel therapeutic option in CD that deserves further investigation.

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IL-10 is significantly involved in HSP70-regulation of experimental subretinal fibrosis.

Publications

IL-10 is significantly involved in HSP70-regulation of experimental subretinal fibrosis.

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