Journal
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
Volume 53, Issue 8, Pages 4396-4406Publisher
ASSOC RESEARCH VISION OPHTHALMOLOGY INC
DOI: 10.1167/iovs.12-9724
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- Azrieli Fellowship from the Azrieli Foundation in Israel
- Chief Scientist Office of the Ministry of Health, Israel [7803]
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PURPOSE. Systemic polyunsaturated fatty acids (PUFAs) were shown to improve the symptoms of dry eye syndrome due to their anti-inflammatory effects. This study evaluated the in vitro anti-inflammatory effects of PUFAs on human corneal epithelial (HCE) cells. METHODS. HCE cells were incubated for 2 hours with different concentrations of PUFAs: alpha-linolenic acid (ALA), gamma-linolenic acid (GLA), and linoleic acid (LA). Oleic acid (OA) and dexamethasone (DM) served as negative and positive controls, respectively. Cells were stimulated with either polyinosinic: polycytidylic acid (poly I:C) or lipopolysaccharide (LPS) complex. The protein contents and mRNA expression levels of IL-6, IL-8, IL-1 beta, and TNF-alpha were evaluated with multiplex fluorescent bead immunoassay and real-time PCR, respectively. The expression of inhibitory factor-kappa B alpha (I-kappa B alpha) was evaluated with real-time PCR. RESULTS. The protein and mRNA levels of IL-6, IL-8, IL-1 beta, and TNF-alpha were significantly increased after stimulation with LPS or poly I:C. Following treatment with ALA, a significant decrease was demonstrated in the protein content of TNF-alpha to 23.81% (P < 0.001), IL-6 to 46.71% (P < 0.001), IL-1 beta to 20.86% (P < 0.05), and IL-8 to 52.21% (P < 0.001). Similar results were demonstrated at the mRNA level. The anti-inflammatory effects of ALA were similar to those of DM for all of the pro-inflammatory cytokines. The ALA inhibition of the pro-inflammatory cytokines was associated with a significant reduction of I-kappa B alpha. CONCLUSIONS. ALA may serve as a potent anti-inflammatory agent in ocular surface inflammation. The anti-inflammatory effects of ALA are comparable to those of corticosteroids, and are mediated through NF-kappa B signal transduction. (Invest Ophthalmol Vis Sci. 2012;53:4396-4406) DOI:10.1167/iovs.12-9724
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