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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2019

Open Access 01-12-2019 | Uveitis | Research

KS23, a novel peptide derived from adiponectin, inhibits retinal inflammation and downregulates the proportions of Th1 and Th17 cells during experimental autoimmune uveitis

Authors: Tian Niu, Lu Cheng, Hanying Wang, Shaopin Zhu, Xiaolu Yang, Kun Liu, Huiyi Jin, Xun Xu

Published in: Journal of Neuroinflammation | Issue 1/2019

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Abstract

Background

Uveitis is a potentially sight-threatening form of ocular inflammation that affects the uvea in the wall of the eye. Currently available treatments for uveitis have exhibited profound adverse side effects. However, KS23 is a novel 23-amino-acid anti-inflammatory peptide derived from adiponectin that may have the capability to function as a safe alternative to these existing treatment options. We, therefore, evaluated the preventive effect of KS23 in experimental autoimmune uveitis (EAU).

Methods

EAU was induced in mice via immunization with the peptide interphotoreceptor retinoid binding protein 161–180 (IRBP161–180). KS23 was then administered every 2 days via intraperitoneal injection to induce protection against EAU. Clinical and histopathological scores were employed to evaluate the disease progression. Inflammatory cytokines were also quantified using ELISA, and the expression levels of specific chemokines and chemokine receptors were assessed via qRT-PCR. In addition, the proportions of Th1 and Th17 cells were detected via flow cytometry, and the expression levels of specific proteins were quantified from the retina of mice using western blot analysis, to elucidate the specific mechanism of action employed by KS23 to suppress the inflammation associated with EAU.

Results

KS23 was found to significantly improve EAU-associated histopathological scores, while decreasing the expression of pro-inflammatory cytokines (IFN-γ, TNF-α, IL-6, and IL-17A), chemokines (LARC, RANTES, MIG, IP-10), and chemokine receptors (CCR6 and CXCR3). The proportions of Th1 and Th17 cells were also suppressed following intraperitoneal injection with KS23. The anti-inflammatory mechanism employed by KS23 was determined to be associated with the activation of AMPK and subsequent inhibition of NF-κB.

Conclusions

KS23 decreased the proportions of Th1 and Th17 cells to effectively ameliorate the progression of EAU. It may, therefore, serve as a promising potential therapeutic agent for uveitis.
Appendix
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Metadata
Title
KS23, a novel peptide derived from adiponectin, inhibits retinal inflammation and downregulates the proportions of Th1 and Th17 cells during experimental autoimmune uveitis
Authors
Tian Niu
Lu Cheng
Hanying Wang
Shaopin Zhu
Xiaolu Yang
Kun Liu
Huiyi Jin
Xun Xu
Publication date
01-12-2019
Publisher
BioMed Central
Keyword
Uveitis
Published in
Journal of Neuroinflammation / Issue 1/2019
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-019-1686-y

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