A cholinergic agonist attenuates endotoxin-induced uveitis in rats.
OBJECTIVE
Investigation of physiological anti-inflammatory mechanisms can contribute to the treatment of inflammatory disorders. The purpose of the present study was to investigate the effect of nicotine, a selective cholinergic agonist, on endotoxin-induced uveitis (EIU) in rats and the underlying molecular mechanism.


METHODS
Lipopolysaccharide (LPS; endotoxin) and nicotine were injected intraperitoneally. Clinical scores were evaluated by slit lamp. Intracameral protein content and the number of cells were determined. Immunohistochemical reactivity of alpha7 nicotine acetylcholine receptor (alpha7nAChR) was examined in the iris and ciliary body (ICB). mRNA and protein levels of cytokines and chemokines were measured by real-time PCR and enzyme-linked immunosorbent assay.


RESULTS
After LPS injection, clinical scores, as well as protein content and number of cells in the aqueous humor increased during 18 to 36 hours. Nicotine inhibited the endotoxin-induced elevation of these levels. mRNA and protein of alpha7nAChR expression levels were significantly increased by LPS and/or nicotine injection. Nicotine showed no effects on endotoxin-induced elevation of mRNA levels in ICB. However, nicotine decreased the endotoxin-induced elevation of interleukin (IL)-6, IL-1beta, tumor necrosis factor (TNF)-alpha, cytokine-induced neutrophil chemoattractant (CINC)-1, and monocyte chemotactic protein (MCP)-1, but did not affect IL-10 in the serum and aqueous humor.


CONCLUSIONS
Nicotine attenuated endotoxin-induced uveitis through directly decreasing the levels of multiple cytokines and chemokines in the aqueous humor, but did not affect the mRNA levels of these factors. The findings suggest that the nicotinic anti-inflammatory pathway may be involved in the pathogenesis of EIU.
Chi
Zai-Long
ZL
Department of Ophthalmology, Graduate School of Medicine, University of Toyama, Toyama, Japan. ophthal@med.u-toyama.ac.jp
Hayasaka
Seiji
S
Zhang
Xue-Yun
XY
Cui
Hu-Shan
HS
Hayasaka
Yoriko
Y
D000818:Animals; D001082:Aqueous Humor / Q000166:cytology / Q000378:metabolism; D002924:Ciliary Body / Q000378:metabolism; D016207:Cytokines / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D004926:Escherichia coli; D007274:Injections, Intraperitoneal; D007498:Iris / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity*; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014605:Uveitis / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D064569:alpha7 Nicotinic Acetylcholine Receptor
C579165:Chrna7 protein, rat; D016207:Cytokines; D008070:Lipopolysaccharides; D018722:Nicotinic Agonists; D012333:RNA, Messenger; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; D009538:Nicotine