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Dry eye management in a Sjögren’s syndrome mouse model by inhibition of p38-MAPK pathway

Xiaoyun Ma1, Jun Zou2*, Linping He1 and Yun Zhang3*

Author Affiliations

1 Department of Ophthalmology, Guanghua Integrative Medicine Hospital, Shanghai, Changning District, China

2 Department of Ophthalmology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China

3 Institute of Arthritis Research, Shanghai Academy of Chinese Medical Sciences, Shanghai, China

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Diagnostic Pathology 2014, 9:5  doi:10.1186/1746-1596-9-5

Published: 20 January 2014



To investigate the therapeutic effect of p38-MAPK inhibitor, SB203580, on dry eye in a mouse model of Sjögren’s syndrome (MRL/lpr mice).


18 female BALB/c mice and 44 female MRL/lpr mice were included. Mice were randomly assigned to the control or treatment group. The expression of phospho-p38 MAPK in lacrimal glands of BALB/c mice was determined by Western blot analysis following IL-1β treatment at various time points. Different doses of SB203580 were injected into lacrimal glands of MRL/lpr mice and phenol red thread test was performed seven days post-injection. Moreover, the levels of acetylcholine and norepinephrine expression in lacrimal glands of MRL/lpr mice were measured using spectrofluoremetric assay and the histopathology of lacrimal glands was also evaluated.


The expression of p-p38 MAPK in lacrimal glands of BALB/c mice gradually increased following incubation with IL-1β ex vivo. Injection of SB203580 into lacrimal glands significantly improved the results of phenol red thread test in MRL/lpr mice. In addition, the secretions of acetylcholine and norepinephrine increased significantly compared to the control group. Less lymphocytes infiltration was observed in pathological section of lacrimal glands following SB203580 injection.


Our results indicate that the activation of p38-MAPK pathway plays an important role in dry eye of a Sjögren’s syndrome mouse model. Inhibition of p38-MAPK pathway by SB203580 might have potential therapeutic effect on Sjögren’s syndrome associated dry eye.

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Sjögren’s syndrome; Dry eye; Interleukin-1β; p38-MAPK pathway