Tacrolimus downregulates inflammation by regulating pro‑/anti‑inflammatory responses in LPS‑induced keratitis

Yu,Yifeng; Zhong,Jing; Peng,Lulu; Wang,Bowen; Li,Saiqun; Huang,Haixiang; Deng,Yuqing; Zhang,Henan; Yang,Ruhui; Wang,Changyun; Yuan,Jin

doi:10.3892/mmr.2017.7353

Tacrolimus downregulates inflammation by regulating pro‑/anti‑inflammatory responses in LPS‑induced keratitis

Authors:
- Yifeng Yu
- Jing Zhong
- Lulu Peng
- Bowen Wang
- Saiqun Li
- Haixiang Huang
- Yuqing Deng
- Henan Zhang
- Ruhui Yang
- Changyun Wang
- Jin Yuan
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Affiliations: Department of Ophthalmology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat‑Sen University, Guangzhou, Guangdong 510064, P.R. China
Published online on: August 24, 2017 https://doi.org/10.3892/mmr.2017.7353
Pages: 5855-5862
Copyright: © Yu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Lipopolysaccharide (LPS)‑induced keratitis is a progressive infectious ocular disease in which innate inflammatory responses often cause clinical tissue damage and vision loss. The present study aimed to investigate the effects of tacrolimus, an effective immunomodulator, on LPS‑induced innate immune responses. The effects of tacrolimus on the apoptotic rate and viability of human corneal epithelial cells (HCECs), polymorphonuclear neutrophils (PMNs) and monocytes (THP‑1 cells) were examined using flow cytometry and MTT assays. Subsequently, the role of tacrolimus on LPS‑induced inflammation in HCECs, PMNs and THP‑1 cells was evaluated by detecting the expression levels of pro‑inflammatory cytokines, including interleukin (IL)‑1β, IL‑6 and matrix metallopeptidase 9; anti‑inflammatory cytokines, including IL‑10 and transforming growth factor‑β; and proangiogenic factors, including vascular endothelial growth factor and tumor necrosis factor‑α using quantitative polymerase chain reaction. The results demonstrated that tacrolimus had good biocompatibility with HCECs, while promoting apoptosis and decreasing the viability of PMNs and THP‑1 cells. Furthermore, tacrolimus effectively reduced the expression levels of pro‑inflammatory cytokines and increased anti‑inflammatory cytokines in LPS‑induced keratitis in vitro. Notably, tacrolimus decreased the levels of proangiogenic factors, which are highly increased following LPS stimulation. Conclusively, tacrolimus appears to be a safe and effective treatment to suppress neutrophil and monocyte activity, modulate the balance of pro‑/anti‑inflammatory cytokines, and reduce the inflammatory response and angiogenic activity in LPS‑induced bacterial keratitis.

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