» Articles » PMID: 34204067

Hydroquinone Induces NLRP3-Independent IL-18 Release from ARPE-19 Cells

Overview
Journal Cells
Publisher MDPI
Date 2021 Jul 2
PMID 34204067
Citations 5
Authors
Affiliations
Soon will be listed here.
Abstract

Age-related macular degeneration (AMD) is a retinal disease leading to impaired vision. Cigarette smoke increases the risk for developing AMD by causing increased reactive oxygen species (ROS) production and damage in the retinal pigment epithelium (RPE). We have previously shown that the cigarette tar component hydroquinone causes oxidative stress in human RPE cells. In the present study, we investigated the propensity of hydroquinone to induce the secretion of interleukin (IL)-1β and IL-18. The activation of these cytokines is usually regulated by the Nucleotide-binding domain, Leucine-rich repeat, and Pyrin domain 3 (NLRP3) inflammasome. ARPE-19 cells were exposed to hydroquinone, and cell viability was monitored using the lactate dehydrogenase (LDH) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide salt (MTT) assays. Enzyme-linked immunosorbent assays (ELISAs) were used to measure the levels of proinflammatory cytokines IL-1β and IL-18 as well as NLRP3, caspase-1, and poly (ADP-ribose) polymerase (PARP). Hydroquinone did not change IL-1β release but significantly increased the secretion of IL-18. Cytoplasmic NLRP3 levels increased after the hydroquinone treatment of IL-1α-primed RPE cells, but IL-18 was equally released from primed and nonprimed cells. Hydroquinone reduced the intracellular levels of PARP, which were restored by treatment with the ROS scavenger N-acetyl-cysteine (NAC). NAC concurrently reduced the NLRP3 levels but had no effect on IL-18 release. In contrast, the NADPH oxidase inhibitor ammonium pyrrolidinedithiocarbamate (APDC) reduced the release of IL-18 but had no effect on the NLRP3 levels. Collectively, hydroquinone caused DNA damage seen as reduced intracellular PARP levels and induced NLRP3-independent IL-18 secretion in human RPE cells.

Citing Articles

Effects on Iron Metabolism and System Xc- /GPX4 Pathway from Hydroquinone Suggest Ferroptosis of Jurkat Cells.

Liu N, Liu G, Li Q, Hu Y, Wang H Toxics. 2024; 12(9).

PMID: 39330572 PMC: 11436165. DOI: 10.3390/toxics12090644.


NLRP3 and autophagy in retinal ganglion cell inflammation in age-related macular degeneration: potential therapeutic implications.

Wang X, Gao Y, Yuan Q, Zhang M Int J Ophthalmol. 2024; 17(8):1531-1544.

PMID: 39156786 PMC: 11286452. DOI: 10.18240/ijo.2024.08.20.


Anti-inflammatory potential of simvastatin and amfenac in ARPE-19 cells; insights in preventing re-detachment and proliferative vitreoretinopathy after rhegmatogenous retinal detachment surgery.

Harju N, Hytti M, Kolari O, Nisula H, Loukovaara S, Kauppinen A Int Ophthalmol. 2024; 44(1):158.

PMID: 38530532 PMC: 10965607. DOI: 10.1007/s10792-024-03067-z.


Spotlight on pyroptosis: role in pathogenesis and therapeutic potential of ocular diseases.

Chen M, Rong R, Xia X J Neuroinflammation. 2022; 19(1):183.

PMID: 35836195 PMC: 9281180. DOI: 10.1186/s12974-022-02547-2.


Hydroquinone predisposes for retinal pigment epithelial (RPE) cell degeneration in inflammatory conditions.

Bhattarai N, Hytti M, Reinisalo M, Kaarniranta K, Mysore Y, Kauppinen A Immunol Res. 2022; 70(5):678-687.

PMID: 35661979 PMC: 9499922. DOI: 10.1007/s12026-022-09300-0.

References
1.
Kauppinen A, Niskanen H, Suuronen T, Kinnunen K, Salminen A, Kaarniranta K . Oxidative stress activates NLRP3 inflammasomes in ARPE-19 cells--implications for age-related macular degeneration (AMD). Immunol Lett. 2012; 147(1-2):29-33. DOI: 10.1016/j.imlet.2012.05.005. View

2.
Gao J, Liu R, Cao S, Cui J, Wang A, To E . NLRP3 inflammasome: activation and regulation in age-related macular degeneration. Mediators Inflamm. 2015; 2015:690243. PMC: 4324923. DOI: 10.1155/2015/690243. View

3.
Lee J, Yang E, Kim I . Hydroquinone-induced apoptosis of human lymphocytes through caspase 9/3 pathway. Mol Biol Rep. 2012; 39(6):6737-43. DOI: 10.1007/s11033-012-1498-y. View

4.
Tarallo V, Hirano Y, Gelfand B, Dridi S, Kerur N, Kim Y . DICER1 loss and Alu RNA induce age-related macular degeneration via the NLRP3 inflammasome and MyD88. Cell. 2012; 149(4):847-59. PMC: 3351582. DOI: 10.1016/j.cell.2012.03.036. View

5.
Fujihara M, Nagai N, Sussan T, Biswal S, Handa J . Chronic cigarette smoke causes oxidative damage and apoptosis to retinal pigmented epithelial cells in mice. PLoS One. 2008; 3(9):e3119. PMC: 2518621. DOI: 10.1371/journal.pone.0003119. View