Unknown

Dataset Information

0

Interleukin-20 is involved in dry eye disease and is a potential therapeutic target.


ABSTRACT:

Background

Dry eye disease (DED) is a common disease in ophthalmology, affecting millions of people worldwide. Recent studies have shown that inflammation is the core mechanism of DED. IL-20 is a proinflammatory cytokine involved in various inflammatory diseases. Therefore, we aimed to explore the role of this cytokine in the pathogenesis of DED and evaluate the therapeutic potential of the anti-IL-20 monoclonal antibody (mAb) 7E for DED treatment.

Methods

Clinical tear samples from patients with DED and non-DED controls were collected and their IL-20 protein levels were determined. We established three DED animal models to explore the role of IL-20 and the efficacy of IL-20 antibody in DED. Benzalkonium chloride (BAC)-induced over-evaporative DED, extra-orbital lacrimal gland excision (LGE)-induced aqueous tear-deficient DED, and desiccating stress (DS)-induced combined over-evaporative and aqueous tear-deficient DED animal models were established to investigate the role of IL-20. The anti-IL-20 antibody 7E was established to neutralize IL-20 activity. The effects of IL-20 or 7E on human corneal epithelial cells and macrophages under hyperosmotic stress were analyzed. 7E was topically applied to eyes to evaluate the therapeutic effects in the DED animal models.

Results

IL-20 was significantly upregulated in the tears of patients with DED and in the tears and corneas of DED animal models. Under hyperosmotic stress, IL-20 expression was induced via NFAT5 activation in corneal epithelial cells. 7E suppressed hyperosmotic stress-induced activation of macrophages. IL-20 induced cell death in corneal epithelial cells and 7E protected cells from hyperosmotic stress-induced cell death. Blocking IL-20 signaling with 7E protected mice from BAC-induced, LGE-induced, and DS-induced DED by reducing DED symptoms and inhibiting inflammatory responses, macrophage infiltration, apoptosis, and Th17 populations in the conjunctiva and draining lymph nodes.

Conclusions

Our results demonstrated the functions of IL-20 in DED and presented a potential therapeutic option for this condition.

SUBMITTER: Wang HH 

PROVIDER: S-EPMC9178884 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

altmetric image

Publications

Interleukin-20 is involved in dry eye disease and is a potential therapeutic target.

Wang Hsiao-Hsuan HH   Chen Wei-Yu WY   Huang Yi-Hsun YH   Hsu Sheng-Min SM   Tsao Yeou-Ping YP   Hsu Yu-Hsiang YH   Chang Ming-Shi MS  

Journal of biomedical science 20220609 1


<h4>Background</h4>Dry eye disease (DED) is a common disease in ophthalmology, affecting millions of people worldwide. Recent studies have shown that inflammation is the core mechanism of DED. IL-20 is a proinflammatory cytokine involved in various inflammatory diseases. Therefore, we aimed to explore the role of this cytokine in the pathogenesis of DED and evaluate the therapeutic potential of the anti-IL-20 monoclonal antibody (mAb) 7E for DED treatment.<h4>Methods</h4>Clinical tear samples fr  ...[more]

Similar Datasets

| S-EPMC11751114 | biostudies-literature
| S-EPMC5240001 | biostudies-literature
| S-EPMC5913811 | biostudies-literature
| S-EPMC10843105 | biostudies-literature
| S-EPMC10573358 | biostudies-literature
| S-EPMC9556763 | biostudies-literature
| S-EPMC7794831 | biostudies-literature
| S-EPMC4167802 | biostudies-literature
2022-12-19 | GSE182582 | GEO
| S-EPMC10323053 | biostudies-literature