interleukin-8 and Retinal-Diseases

4-Hydroxynonenal (HNE) is a highly reactive end-product of lipid peroxidation reaction that leads to retinal pigment epithelial (RPE) cell damage. Cyanidin-3-glucoside (C3G), the most abundant anthocyanin in the edible parts of plants, is a nutritional supplement used for preventing retinal damage. However, the protective effect of C3G against HNE-induced RPE cell damage remains to be elucidated. The protective mechanisms of C3G on ARPE-19 cells after HNE exposure were investigated in this study. Results showed that compared with HNE-treated cells, the viability of ARPE-19 cells was significantly (P < 0.05) increased after 1 and 5 μM C3G treatment. C3G exhibited a significant (P < 0.05) inhibitory effect on the expression of senescence-associated β-galactosidase in ARPE-19 cells. VEGF levels in the C3G groups were significantly (P < 0.05) decreased relative to those of the HNE-treated group. C3G also regulated the release of two inflammatory mediators, namely monocyte chemoattractant protein 1 and interleukine-8, in ARPE-19 cells after HNE treatment. Furthermore, C3G attenuated retinal cell apoptosis in pigmented rabbits induced by visible light. Therefore, our data showed that C3G has efficient protective effects on HNE-induced apoptosis, angiogenesis, and dysregulated cytokine production in ARPE-19 cells.

Topics: Aldehydes; Animals; Anthocyanins; Apoptosis; Chemokine CCL2; Glucosides; Humans; Interleukin-8; Light; Rabbits; Retinal Diseases; Retinal Pigment Epithelium; Vascular Endothelial Growth Factor A

The effects of administering omega-3 (ω-3) polyunsaturated fatty acid (PUFA)-rich oils on visible-light-induced retinal damage were investigated in rabbits. The mole percentages of α-linolenic acid in sea buckthorn berry oil, sea buckthorn oil (SO), sea buckthorn seed oil and flaxseed oil (FO) were 2.12%, 12.98%, 31.56% and 55.41%, respectively. Algal oil (AO) contains 33.34% docosahexaenoic acid. SO has the highest total phenolic content (63.42 ± 0.59 mg SAE per 100 g) amongst these oils. The administration of SO, FO and AO provided structural and functional protection to the retina. In the retina, we observed a significant increase in the levels of DHA in the AO group compared with the normal group. The mechanism of retinal protection by SO, FO and AO involves up-regulating the expression of nuclear factor erythroid-2 related factor 2 and haem oxygenase-1. The levels of interleukin-1 β, tumour necrosis factor-alpha, interleukin-8, and cyclooxygenase 2 in the retina were significantly reduced with AO treatment. The administration of AO resulted in the down-regulation of nuclear factor kappa B mRNA expression. In addition, the treatment with AO significantly attenuated the light-induced apoptosis and angiogenesis in the retina. These results suggest that dietary ω-3 PUFA-rich oils protect against visible-light-induced retinal damage.

Topics: Animals; Dietary Supplements; Fatty Acids, Omega-3; Heme Oxygenase-1; Humans; Interleukin-1; Interleukin-8; Light; NF-E2 Transcription Factor; Rabbits; Retina; Retinal Diseases; Tumor Necrosis Factor-alpha

Argon has recently come into scientific focus as a neuroprotective agent. The underlying neuroprotective mechanism remains unknown although toll-like receptors were recently suggested to play an important role. We hypothesized that TLR-associated downstream transcription factors are responsible for argon's effects, leading to anti-apoptotic and anti-inflammatory properties. Apoptosis was induced in human neuroblastoma cells. Immediately afterwards, argon treatment (75 Vol% for 2 h) was initiated. Cells were analyzed, measuring mitochondrial membrane potential, reactive-oxygen-species, annexin-V/propidium iodide staining, transcription factor phosphorylation and binding activity as well as protein and mRNA expression of interleukins. Argon's in vivo effects were analyzed by quantification of retinal ganglion cell density, mRNA expression, serum cytokine analysis and immunohistochemistry after retinal ischemia reperfusion injury (IRI) in rats. Argon diminished rotenone-induced kappa-light-chain-enhancer' of activated B-cells (NF-κB) and signal transducer and activator of transcription 3 (STAT3) but not STAT5 or cAMP-response element-binding protein (CREB) phosphorylation and DNA-binding activity. Argon treatment attenuated apoptosis by preservation of mitochondrial membrane potential and decline in reactive oxygen species (ROS) generation. NF-κB and STAT3 inhibition, as well as TLR2 and TLR4 inhibition reversed argon's effects on IL-8 mRNA expression. Argon attenuated rotenone-induced IL-8 protein and mRNA expression in vitro. Inhibition of TLR2 and 4 attenuated argon's protective effect in vivo reducing IRI driven retinal IL-8 expression. IL-8 expression was found in the retina in co-localization with Müller cells and retinal ganglion cells. Argon mediates its neuroprotective effects by TLR-mediated regulation of transcription factors NF-κB and STAT3, thus decreasing interleukin-8 expression in vitro and in vivo. These findings may open up new opportunities to effectively treat cerebral ischemia and reperfusion injury through the inhalation of argon. Argon exerts its protective effects in vitro and in vivo via toll-like receptors TLR2 and TLR4 signaling, followed by alteration of downstream enzymes. In conclusion, argon mediates its beneficial effects by suppression of STAT3 and NF-κB phosphorylation and subsequent suppression of interleukin IL-8 protein expression. These novel findings may open up opportunities for argon as a therapeutic agent, particular

Topics: Animals; Apoptosis; Argon; Female; Humans; Interleukin-8; Male; Membrane Potential, Mitochondrial; Neuroblastoma; Neuroprotective Agents; NF-kappa B; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Reperfusion Injury; Retinal Diseases; Signal Transduction; STAT3 Transcription Factor; Toll-Like Receptor 2; Toll-Like Receptor 4

To investigate whether the cytokine interleukin-8 (IL-8), a strong chemoattractant and activator for neutrophils, is responsible for neutrophil infiltration and degranulation in the eye in uveitis.. IL-8 and elastase were measured with specific enzyme-linked immunoassays in vitreous fluid samples obtained from 69 patients with various uveitis entities. Vitreous fluid of nonuveitis patients and eye bank eyes served as controls. The chemotactic activity of vitreous fluid was tested with the Boyden chamber technique.. IL-8 was detected in 45% of the vitreous fluid samples from uveitis patients and in 26% of vitreous fluid samples from nonuveitis patients. Vitreous fluid samples with IL-8 levels exceeding 100 pg/ml were chemotactic for neutrophils. This chemotactic activity could be blocked by 41% to 79% with a monoclonal anti-IL-8 antibody. Elastase levels in vitreous fluid of uveitis patients with detectable IL-8 were significantly higher than those in vitreous fluid samples with no detectable IL-8.. These results indicate that IL-8 participates in the inflammatory processes in the eye by attracting and degranulating neutrophils. It is suggested that these processes contribute to the pathogenesis of tissue destruction in uveitis.

Topics: Cell Degranulation; Cells, Cultured; Chemotaxis, Leukocyte; Enzyme-Linked Immunosorbent Assay; Eye Diseases; Humans; Interleukin-8; Neutrophils; Pancreatic Elastase; Retinal Diseases; Uveitis; Vitreous Body