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Fisetin and luteolin protect human retinal pigment epithelial cells from oxidative stress-induced cell death and regulate inflammation.

Hytti M, Piippo N, Korhonen E, Honkakoski P, Kaarniranta K, Kauppinen A - Sci Rep (2015)

Bottom Line: Here, we assess the ability of fisetin and luteolin, to protect ARPE-19 cells from oxidative stress-induced cell death and to decrease intracellular inflammation.The decrease in inflammation was associated with reduced activation of MAPKs and CREB, but was not linked to NF- κB or SIRT1.The ability of fisetin and luteolin to protect and repair stressed RPE cells even after the oxidative insult make them attractive in the search for treatments for AMD.

View Article: PubMed Central - PubMed

Affiliation: School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, P.O.B. 1627, FI-70211, Kuopio, Finland.

ABSTRACT
Degeneration of retinal pigment epithelial (RPE) cells is a clinical hallmark of age-related macular degeneration (AMD), the leading cause of blindness among aged people in the Western world. Both inflammation and oxidative stress are known to play vital roles in the development of this disease. Here, we assess the ability of fisetin and luteolin, to protect ARPE-19 cells from oxidative stress-induced cell death and to decrease intracellular inflammation. We also compare the growth and reactivity of human ARPE-19 cells in serum-free and serum-containing conditions. The absence of serum in the culture medium did not prevent ARPE-19 cells from reaching full confluency but caused an increased sensitivity to oxidative stress-induced cell death. Both fisetin and luteolin protected ARPE-19 cells from oxidative stress-induced cell death. They also significantly decreased the release of pro-inflammatory cytokines into the culture medium. The decrease in inflammation was associated with reduced activation of MAPKs and CREB, but was not linked to NF- κB or SIRT1. The ability of fisetin and luteolin to protect and repair stressed RPE cells even after the oxidative insult make them attractive in the search for treatments for AMD.

No MeSH data available.


Related in: MedlinePlus

Effect of fisetin and luteolin on the release of cytokines from HNE-treated serum-starved ARPE-19 cells.Both fisetin and luteolin decreased the release of the cytokines IL-6 (a), IL-8 (b), and MCP-1 (c) from ARPE-19 cells when compared to cells exposed to HNE and the solvent DMSO. Results are shown as scatterplots with median and are combined from 5–20 independent experiments with 3–4 parallel determinations per group/experiment. ***denotes p < 0.001, Mann–Whitney U-test.
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f4: Effect of fisetin and luteolin on the release of cytokines from HNE-treated serum-starved ARPE-19 cells.Both fisetin and luteolin decreased the release of the cytokines IL-6 (a), IL-8 (b), and MCP-1 (c) from ARPE-19 cells when compared to cells exposed to HNE and the solvent DMSO. Results are shown as scatterplots with median and are combined from 5–20 independent experiments with 3–4 parallel determinations per group/experiment. ***denotes p < 0.001, Mann–Whitney U-test.

Mentions: In addition to reduced cellular viability, the exposure of serum-starved ARPE-19 cells to 30 μM HNE decreased the levels of IL-6, IL-8, and MCP-1 when compared to unexposed control cells (Fig. 4). Still, both fisetin and luteolin further decreased the release of IL-6, IL-8, and MCP-1 from HNE-exposed ARPE-19 cells (Fig. 4). The response was highly statistically significant (p < 0.0001 for both fisetin and luteolin in each of the cytokines studied) and lowered the overall levels of released pro-inflammatory cytokines to close to the detection limit. The reduction in IL-6 and IL-8 levels was also observed in fully differentiated ARPE-19 cells cultured for 4 weeks on laminin-coated filter-wells, suggesting that fisetin and luteolin are effective anti-inflammatory agents in both undifferentiated and fully differentiated cells. (Suppl. Fig. 3). The effect of HNE treatment on IL-6, IL-8 or MCP-1 levels was not affected by the polyphenol solvent DMSO (Fig. 4). Therefore, HNE + DMSO-treated cells were chosen to serve as controls to the effects of fisetin and luteolin in this and all subsequent experiments.


Fisetin and luteolin protect human retinal pigment epithelial cells from oxidative stress-induced cell death and regulate inflammation.

Hytti M, Piippo N, Korhonen E, Honkakoski P, Kaarniranta K, Kauppinen A - Sci Rep (2015)

Effect of fisetin and luteolin on the release of cytokines from HNE-treated serum-starved ARPE-19 cells.Both fisetin and luteolin decreased the release of the cytokines IL-6 (a), IL-8 (b), and MCP-1 (c) from ARPE-19 cells when compared to cells exposed to HNE and the solvent DMSO. Results are shown as scatterplots with median and are combined from 5–20 independent experiments with 3–4 parallel determinations per group/experiment. ***denotes p < 0.001, Mann–Whitney U-test.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4664957&req=5

f4: Effect of fisetin and luteolin on the release of cytokines from HNE-treated serum-starved ARPE-19 cells.Both fisetin and luteolin decreased the release of the cytokines IL-6 (a), IL-8 (b), and MCP-1 (c) from ARPE-19 cells when compared to cells exposed to HNE and the solvent DMSO. Results are shown as scatterplots with median and are combined from 5–20 independent experiments with 3–4 parallel determinations per group/experiment. ***denotes p < 0.001, Mann–Whitney U-test.
Mentions: In addition to reduced cellular viability, the exposure of serum-starved ARPE-19 cells to 30 μM HNE decreased the levels of IL-6, IL-8, and MCP-1 when compared to unexposed control cells (Fig. 4). Still, both fisetin and luteolin further decreased the release of IL-6, IL-8, and MCP-1 from HNE-exposed ARPE-19 cells (Fig. 4). The response was highly statistically significant (p < 0.0001 for both fisetin and luteolin in each of the cytokines studied) and lowered the overall levels of released pro-inflammatory cytokines to close to the detection limit. The reduction in IL-6 and IL-8 levels was also observed in fully differentiated ARPE-19 cells cultured for 4 weeks on laminin-coated filter-wells, suggesting that fisetin and luteolin are effective anti-inflammatory agents in both undifferentiated and fully differentiated cells. (Suppl. Fig. 3). The effect of HNE treatment on IL-6, IL-8 or MCP-1 levels was not affected by the polyphenol solvent DMSO (Fig. 4). Therefore, HNE + DMSO-treated cells were chosen to serve as controls to the effects of fisetin and luteolin in this and all subsequent experiments.

Bottom Line: Here, we assess the ability of fisetin and luteolin, to protect ARPE-19 cells from oxidative stress-induced cell death and to decrease intracellular inflammation.The decrease in inflammation was associated with reduced activation of MAPKs and CREB, but was not linked to NF- κB or SIRT1.The ability of fisetin and luteolin to protect and repair stressed RPE cells even after the oxidative insult make them attractive in the search for treatments for AMD.

View Article: PubMed Central - PubMed

Affiliation: School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, P.O.B. 1627, FI-70211, Kuopio, Finland.

ABSTRACT
Degeneration of retinal pigment epithelial (RPE) cells is a clinical hallmark of age-related macular degeneration (AMD), the leading cause of blindness among aged people in the Western world. Both inflammation and oxidative stress are known to play vital roles in the development of this disease. Here, we assess the ability of fisetin and luteolin, to protect ARPE-19 cells from oxidative stress-induced cell death and to decrease intracellular inflammation. We also compare the growth and reactivity of human ARPE-19 cells in serum-free and serum-containing conditions. The absence of serum in the culture medium did not prevent ARPE-19 cells from reaching full confluency but caused an increased sensitivity to oxidative stress-induced cell death. Both fisetin and luteolin protected ARPE-19 cells from oxidative stress-induced cell death. They also significantly decreased the release of pro-inflammatory cytokines into the culture medium. The decrease in inflammation was associated with reduced activation of MAPKs and CREB, but was not linked to NF- κB or SIRT1. The ability of fisetin and luteolin to protect and repair stressed RPE cells even after the oxidative insult make them attractive in the search for treatments for AMD.

No MeSH data available.


Related in: MedlinePlus