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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

Summary of the effects of fisetin and luteolin on serum-starved and HNE-treated ARPE-19 cells.Addition of HNE to serum-starved cells was strongly cytotoxic, and caused decreased release of pro-inflammatory cytokines IL-6 and IL-8 probably trough the inhibition of NF-κB signaling, as discussed previously. Fisetin and luteolin protected the cells from HNE-induced cytotoxicity and induced a strong additional reduction in the IL-6, IL-8, and MCP-1 levels even when added after the HNE exposure. Analysis of signaling protein amounts and phosphorylation levels together with inhibition studies suggest that fisetin and luteolin suppress the release of pro-inflammatory cytokines by decreasing the activation of CREB, JNK, and ERK1/2.
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f9: Summary of the effects of fisetin and luteolin on serum-starved and HNE-treated ARPE-19 cells.Addition of HNE to serum-starved cells was strongly cytotoxic, and caused decreased release of pro-inflammatory cytokines IL-6 and IL-8 probably trough the inhibition of NF-κB signaling, as discussed previously. Fisetin and luteolin protected the cells from HNE-induced cytotoxicity and induced a strong additional reduction in the IL-6, IL-8, and MCP-1 levels even when added after the HNE exposure. Analysis of signaling protein amounts and phosphorylation levels together with inhibition studies suggest that fisetin and luteolin suppress the release of pro-inflammatory cytokines by decreasing the activation of CREB, JNK, and ERK1/2.

Mentions: Overall, fisetin and luteolin show a promising ability to protect RPE cells from oxidative stress-induced cell death and to potently downregulate inflammatory reactions in these cells by decreasing the activity of the transcription factor CREB and the MAPKs p38 MAPK, JNK, and ERK1/2 (Fig. 9). Nonetheless, neither NF-κB nor SIRT1 was involved in the inflammatory regulation. These results offer us valuable insights into the signaling underlying RPE-derived inflammatory reactions and thereby into the pathogenesis of AMD.


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)

Summary of the effects of fisetin and luteolin on serum-starved and HNE-treated ARPE-19 cells.Addition of HNE to serum-starved cells was strongly cytotoxic, and caused decreased release of pro-inflammatory cytokines IL-6 and IL-8 probably trough the inhibition of NF-κB signaling, as discussed previously. Fisetin and luteolin protected the cells from HNE-induced cytotoxicity and induced a strong additional reduction in the IL-6, IL-8, and MCP-1 levels even when added after the HNE exposure. Analysis of signaling protein amounts and phosphorylation levels together with inhibition studies suggest that fisetin and luteolin suppress the release of pro-inflammatory cytokines by decreasing the activation of CREB, JNK, and ERK1/2.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f9: Summary of the effects of fisetin and luteolin on serum-starved and HNE-treated ARPE-19 cells.Addition of HNE to serum-starved cells was strongly cytotoxic, and caused decreased release of pro-inflammatory cytokines IL-6 and IL-8 probably trough the inhibition of NF-κB signaling, as discussed previously. Fisetin and luteolin protected the cells from HNE-induced cytotoxicity and induced a strong additional reduction in the IL-6, IL-8, and MCP-1 levels even when added after the HNE exposure. Analysis of signaling protein amounts and phosphorylation levels together with inhibition studies suggest that fisetin and luteolin suppress the release of pro-inflammatory cytokines by decreasing the activation of CREB, JNK, and ERK1/2.
Mentions: Overall, fisetin and luteolin show a promising ability to protect RPE cells from oxidative stress-induced cell death and to potently downregulate inflammatory reactions in these cells by decreasing the activity of the transcription factor CREB and the MAPKs p38 MAPK, JNK, and ERK1/2 (Fig. 9). Nonetheless, neither NF-κB nor SIRT1 was involved in the inflammatory regulation. These results offer us valuable insights into the signaling underlying RPE-derived inflammatory reactions and thereby into the pathogenesis of AMD.

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