Dry eye management in a Sjögren's syndrome mouse model by inhibition of p38-MAPK pathway.
BACKGROUND
To investigate the therapeutic effect of p38-MAPK inhibitor, SB203580, on dry eye in a mouse model of Sjögren's syndrome (MRL/lpr mice).


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1256849631103092.
Xiaoyun
X
Ma
Department of Ophthalmology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China. zoujun70@126.com.
Jun
J
Zou
Linping
L
He
Yun
Y
Zhang
D000818:Animals; D015153:Blotting, Western; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D007093:Imidazoles / Q000494:pharmacology*; D007765:Lacrimal Apparatus / Q000187:drug effects / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D019463:Mice, Inbred MRL lpr; D011725:Pyridines / Q000494:pharmacology*; D012859:Sjogren's Syndrome / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D004791:Enzyme Inhibitors; D007093:Imidazoles; D011725:Pyridines; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580