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Xiao lu Yang, Hui yi Jin, Xun Xu; A Novel Peptide Inhibits Inflammation in Endotoxin-induced Uveitis by Suppressing NF-kappaB and MAPK Signaling Pathway. Invest. Ophthalmol. Vis. Sci. 2012;53(14):6284.
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The aim of the present study was to investigate the effect of a novel peptide derived from C-type lectin-like domain of human PAP on endotoxin-induced uveitis (EIU) in rats.
EIU was induced in male Wistar rats by a footpad injection of lipopolysaccharide. Peptides or dexamethasone were injected intravitreally an hour before LPS was administered. The rats were killed 3 or 24 hours after LPS injection. Eyes were enucleated for histologic examination, aqueous humor (AqH) was collected, and the number of infiltrating cells, protein concentration, and inflammatory marker levels were determined. The ocular tissue levels of nuclear factor (NF)-kB p65 and phosphorylation levels of p38, ERK 1/2 and JNK were evaluated by Western Blot.
We assessed the anti-inflammatory effect of PAPep on EIU rats and demonstrated that intravitreal pretreatment of PAPep concentration-dependently attenuated clinical manifestation of EIU rats, reduced protein leakage and cell infiltration into the AqH, suppressed TNF-α, IL-6 production in AqH (Figure1), and improved histopathologic manifestation of EIU (Figure2). Furthermore, western blot analysis revealed that the possible mechanism for this anti-inflammatory effect of PAPep may depend on its ability to inhibit the activation of NF-kB and MAPK signaling pathway.
Our studies provide the first evidence that a novel peptide derived from PAP could inhibit inflammation and the peptide may be a promising candidate for the management of ocular inflammatory diseases.
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