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Canagliflozin inhibits inflammasome activation in diabetic endothelial cells – Revealing a novel calcium-dependent anti-inflammatory effect of canagliflozin on human diabetic endothelial cells. / Li, Xiaoling; Kerindongo, Raphaela P.; Preckel, Benedikt et al.

In: Biomedicine and Pharmacotherapy, Vol. 159, 114228, 01.03.2023.

Research output: Contribution to journal › Article › Academic › peer-review

Harvard

Li, X, Kerindongo, RP, Preckel, B, Kalina, J-O, Hollmann, MW, Zuurbier, CJ & Weber, NC 2023, 'Canagliflozin inhibits inflammasome activation in diabetic endothelial cells – Revealing a novel calcium-dependent anti-inflammatory effect of canagliflozin on human diabetic endothelial cells', Biomedicine and Pharmacotherapy, vol. 159, 114228. https://doi.org/10.1016/j.biopha.2023.114228

APA

Li, X., Kerindongo, R. P., Preckel, B., Kalina, J-O., Hollmann, M. W., Zuurbier, C. J., & Weber, N. C. (2023). Canagliflozin inhibits inflammasome activation in diabetic endothelial cells – Revealing a novel calcium-dependent anti-inflammatory effect of canagliflozin on human diabetic endothelial cells. Biomedicine and Pharmacotherapy, 159, [114228]. https://doi.org/10.1016/j.biopha.2023.114228

Vancouver

Li X, Kerindongo RP, Preckel B, Kalina J-O, Hollmann MW, Zuurbier CJ et al. Canagliflozin inhibits inflammasome activation in diabetic endothelial cells – Revealing a novel calcium-dependent anti-inflammatory effect of canagliflozin on human diabetic endothelial cells. Biomedicine and Pharmacotherapy. 2023 Mar 1;159:114228. doi: 10.1016/j.biopha.2023.114228

Author

Li, Xiaoling ; Kerindongo, Raphaela P. ; Preckel, Benedikt et al. / Canagliflozin inhibits inflammasome activation in diabetic endothelial cells – Revealing a novel calcium-dependent anti-inflammatory effect of canagliflozin on human diabetic endothelial cells. In: Biomedicine and Pharmacotherapy. 2023 ; Vol. 159.

BibTeX

@article{fe7f1644e4dd4560a086a43d917410da,
title = "Canagliflozin inhibits inflammasome activation in diabetic endothelial cells – Revealing a novel calcium-dependent anti-inflammatory effect of canagliflozin on human diabetic endothelial cells",
abstract = "Background: Canagliflozin (CANA) shows anti-inflammatory and anti-oxidative effects on endothelial cells (ECs). In diabetes mellitus (DM), excessive reactive oxygen species (ROS) generation, increased intracellular calcium (Ca2+) and enhanced extracellular signal regulated kinase (ERK) 1/2 phosphorylation are crucial precursors for inflammasome activation. We hypothesized that: (1) CANA prevents the TNF-α triggered ROS generation in ECs from diabetic donors and in turn suppresses the inflammasome activation; and (2) the anti-inflammatory effect of CANA is mediated via intracellular Ca2+ and ERK1/2. Methods: Human coronary artery endothelial cells from donors with DM (D-HCAECs) were pre-incubated with either CANA or vehicle for 2 h before exposure to 50 ng/ml TNF-α for 2–48 h. NAC was applied to scavenge ROS, BAPTA-AM to chelate intracellular Ca2+, and PD 98059 to inhibit the activation of ERK1/2. Live cell imaging was performed at 6 h to measure ROS and intracellular Ca2+. At 48 h, ELISA and infra-red western blot were applied to detect IL-1β, NLRP3, pro-caspase-1 and ASC. Results: 10 µM CANA significantly reduced TNF-α related ROS generation, IL-1β production and NLRP3 expression (P all <0.05), but NAC did not alter the inflammasome activation (P > 0.05). CANA and BAPTA both prevented intracellular Ca2+ increase in cells exposed to TNF-α (P both <0.05). Moreover, BAPTA and PD 98059 significantly reduced the TNF-α triggered IL-1β production as well as NLRP3 and pro-caspase-1 expression (P all <0.05). Conclusion: CANA suppresses inflammasome activation by inhibition of (1) intracellular Ca2+ and (2) ERK1/2 phosphorylation, but not by ROS reduction.",
keywords = "Canagliflozin (CANA), Extracellular signal regulated kinase (ERK) 1/2 phosphorylation, Interleukin (IL)− 1β, Intracellular calcium (Ca ), Nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, Reactive oxygen species (ROS)",
author = "Xiaoling Li and Kerindongo, {Raphaela P.} and Benedikt Preckel and Jan-Ole Kalina and Hollmann, {Markus W.} and Zuurbier, {Coert J.} and Weber, {Nina C.}",
note = "Funding Information: X.L. is supported by Chinese Scholarship Council (CSC) fellowship program ( 2019xxxx0054 ). The research received no specific grant from any funding agency in the public, commercial or non-for-profit sectors. Publisher Copyright: {\textcopyright} 2023 The Authors",
year = "2023",
month = mar,
day = "1",
doi = "10.1016/j.biopha.2023.114228",
language = "English",
volume = "159",
journal = "Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie",
issn = "0753-3322",
publisher = "Elsevier Masson",

}

RIS

TY - JOUR

T1 - Canagliflozin inhibits inflammasome activation in diabetic endothelial cells – Revealing a novel calcium-dependent anti-inflammatory effect of canagliflozin on human diabetic endothelial cells

AU - Li, Xiaoling

AU - Kerindongo, Raphaela P.

AU - Preckel, Benedikt

AU - Kalina, Jan-Ole

AU - Hollmann, Markus W.

AU - Zuurbier, Coert J.

AU - Weber, Nina C.

N1 - Funding Information: X.L. is supported by Chinese Scholarship Council (CSC) fellowship program ( 2019xxxx0054 ). The research received no specific grant from any funding agency in the public, commercial or non-for-profit sectors. Publisher Copyright: © 2023 The Authors

PY - 2023/3/1

Y1 - 2023/3/1

N2 - Background: Canagliflozin (CANA) shows anti-inflammatory and anti-oxidative effects on endothelial cells (ECs). In diabetes mellitus (DM), excessive reactive oxygen species (ROS) generation, increased intracellular calcium (Ca2+) and enhanced extracellular signal regulated kinase (ERK) 1/2 phosphorylation are crucial precursors for inflammasome activation. We hypothesized that: (1) CANA prevents the TNF-α triggered ROS generation in ECs from diabetic donors and in turn suppresses the inflammasome activation; and (2) the anti-inflammatory effect of CANA is mediated via intracellular Ca2+ and ERK1/2. Methods: Human coronary artery endothelial cells from donors with DM (D-HCAECs) were pre-incubated with either CANA or vehicle for 2 h before exposure to 50 ng/ml TNF-α for 2–48 h. NAC was applied to scavenge ROS, BAPTA-AM to chelate intracellular Ca2+, and PD 98059 to inhibit the activation of ERK1/2. Live cell imaging was performed at 6 h to measure ROS and intracellular Ca2+. At 48 h, ELISA and infra-red western blot were applied to detect IL-1β, NLRP3, pro-caspase-1 and ASC. Results: 10 µM CANA significantly reduced TNF-α related ROS generation, IL-1β production and NLRP3 expression (P all <0.05), but NAC did not alter the inflammasome activation (P > 0.05). CANA and BAPTA both prevented intracellular Ca2+ increase in cells exposed to TNF-α (P both <0.05). Moreover, BAPTA and PD 98059 significantly reduced the TNF-α triggered IL-1β production as well as NLRP3 and pro-caspase-1 expression (P all <0.05). Conclusion: CANA suppresses inflammasome activation by inhibition of (1) intracellular Ca2+ and (2) ERK1/2 phosphorylation, but not by ROS reduction.

AB - Background: Canagliflozin (CANA) shows anti-inflammatory and anti-oxidative effects on endothelial cells (ECs). In diabetes mellitus (DM), excessive reactive oxygen species (ROS) generation, increased intracellular calcium (Ca2+) and enhanced extracellular signal regulated kinase (ERK) 1/2 phosphorylation are crucial precursors for inflammasome activation. We hypothesized that: (1) CANA prevents the TNF-α triggered ROS generation in ECs from diabetic donors and in turn suppresses the inflammasome activation; and (2) the anti-inflammatory effect of CANA is mediated via intracellular Ca2+ and ERK1/2. Methods: Human coronary artery endothelial cells from donors with DM (D-HCAECs) were pre-incubated with either CANA or vehicle for 2 h before exposure to 50 ng/ml TNF-α for 2–48 h. NAC was applied to scavenge ROS, BAPTA-AM to chelate intracellular Ca2+, and PD 98059 to inhibit the activation of ERK1/2. Live cell imaging was performed at 6 h to measure ROS and intracellular Ca2+. At 48 h, ELISA and infra-red western blot were applied to detect IL-1β, NLRP3, pro-caspase-1 and ASC. Results: 10 µM CANA significantly reduced TNF-α related ROS generation, IL-1β production and NLRP3 expression (P all <0.05), but NAC did not alter the inflammasome activation (P > 0.05). CANA and BAPTA both prevented intracellular Ca2+ increase in cells exposed to TNF-α (P both <0.05). Moreover, BAPTA and PD 98059 significantly reduced the TNF-α triggered IL-1β production as well as NLRP3 and pro-caspase-1 expression (P all <0.05). Conclusion: CANA suppresses inflammasome activation by inhibition of (1) intracellular Ca2+ and (2) ERK1/2 phosphorylation, but not by ROS reduction.

KW - Canagliflozin (CANA)

KW - Extracellular signal regulated kinase (ERK) 1/2 phosphorylation

KW - Interleukin (IL)− 1β

KW - Intracellular calcium (Ca )

KW - Nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome

KW - Reactive oxygen species (ROS)

UR - http://www.scopus.com/inward/record.url?scp=85145687262&partnerID=8YFLogxK

U2 - 10.1016/j.biopha.2023.114228

DO - 10.1016/j.biopha.2023.114228

M3 - Article

C2 - 36623448

VL - 159

JO - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

JF - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

SN - 0753-3322

M1 - 114228

ER -

ID: 30840129