Differential inflammatory responses in cultured endothelial cells exposed to two conjugated linoleic acids (CLAs) under a pro-inflammatory condition
Differential inflammatory responses in cultured endothelial cells exposed to two conjugated linoleic acids (CLAs) under a pro-inflammatory condition
Conjugated linoleic acid (CLA) isomers have been shown to possess anti-atherosclerotic properties, which may be related to the downregulation of inflammatory pathways in different cell types, including endothelial cells (ECs). However, whether different CLA isomers have different actions is not entirely clear, with inconsistent reports to date. Furthermore, in cell culture studies, CLAs have often been used at fairly high concentrations. Whether lower concentrations of CLAs are able to affect EC responses is not clear. The aim of this study was to evaluate the effects of two CLAs (cis-9, trans-11 (CLA9,11) and trans-10, cis-12 (CLA10,12)) on the inflammatory responses of ECs. ECs (EA.hy926 cells) were cultured under standard conditions and exposed to CLAs (1 to 50 μM) for 48 h. Then, the cells were cultured for a further 6 or 24 h with tumour necrosis factor alpha (TNF-α, 1 ng/mL) as an inflammatory stimulant. ECs remained viable after treatments with 1 and 10 μM of each CLA, but not after treatment with 50 μM of CLA10,12. CLAs were incorporated into ECs in a concentration-dependent manner. CLA10,12 increased the levels of ICAM-1, IL-6, and RANTES in the culture medium, while CLA9,11 had null effects. Both CLAs (1 μM) decreased the appearance of NFκB1 mRNA, but only CLA9,11 maintained this downregulation at 10 μM. CLA10,12 had no effect on THP-1 cell adhesion to ECs while significantly decreasing the percentage of ECs expressing ICAM-1 and also levels of ICAM-1 expression per cell when used at 10 µM. Although CLA9,11 did not have any effect on ICAM-1 cell surface expression, it reduced THP-1 cell adhesion to the EA.hy926 cell monolayer at both concentrations. In summary, CLA10,12 showed some pro-inflammatory effects, while CLA9,11 exhibited null or anti-inflammatory effects. The results suggest that each CLA has different effects in ECs under a pro-inflammatory condition, highlighting the need to evaluate the effects of CLA isomers independently.
atherosclerosis, conjugated fatty acids, endothelial cells, inflammation
Valenzuela, Carina
1a12a9b9-6504-4392-90c5-246644b0ad5c
Baker, Ella
7cd5b762-d7d7-4584-b9a7-dba555085440
Miles, Elizabeth
20332899-ecdb-4214-95bc-922dde36d416
Calder, Philip
1797e54f-378e-4dcb-80a4-3e30018f07a6
1 June 2022
Valenzuela, Carina
1a12a9b9-6504-4392-90c5-246644b0ad5c
Baker, Ella
7cd5b762-d7d7-4584-b9a7-dba555085440
Miles, Elizabeth
20332899-ecdb-4214-95bc-922dde36d416
Calder, Philip
1797e54f-378e-4dcb-80a4-3e30018f07a6
Valenzuela, Carina, Baker, Ella, Miles, Elizabeth and Calder, Philip
(2022)
Differential inflammatory responses in cultured endothelial cells exposed to two conjugated linoleic acids (CLAs) under a pro-inflammatory condition.
International Journal of Molecular Sciences, 23 (11), [6101].
(doi:10.3390/ijms23116101).
Abstract
Conjugated linoleic acid (CLA) isomers have been shown to possess anti-atherosclerotic properties, which may be related to the downregulation of inflammatory pathways in different cell types, including endothelial cells (ECs). However, whether different CLA isomers have different actions is not entirely clear, with inconsistent reports to date. Furthermore, in cell culture studies, CLAs have often been used at fairly high concentrations. Whether lower concentrations of CLAs are able to affect EC responses is not clear. The aim of this study was to evaluate the effects of two CLAs (cis-9, trans-11 (CLA9,11) and trans-10, cis-12 (CLA10,12)) on the inflammatory responses of ECs. ECs (EA.hy926 cells) were cultured under standard conditions and exposed to CLAs (1 to 50 μM) for 48 h. Then, the cells were cultured for a further 6 or 24 h with tumour necrosis factor alpha (TNF-α, 1 ng/mL) as an inflammatory stimulant. ECs remained viable after treatments with 1 and 10 μM of each CLA, but not after treatment with 50 μM of CLA10,12. CLAs were incorporated into ECs in a concentration-dependent manner. CLA10,12 increased the levels of ICAM-1, IL-6, and RANTES in the culture medium, while CLA9,11 had null effects. Both CLAs (1 μM) decreased the appearance of NFκB1 mRNA, but only CLA9,11 maintained this downregulation at 10 μM. CLA10,12 had no effect on THP-1 cell adhesion to ECs while significantly decreasing the percentage of ECs expressing ICAM-1 and also levels of ICAM-1 expression per cell when used at 10 µM. Although CLA9,11 did not have any effect on ICAM-1 cell surface expression, it reduced THP-1 cell adhesion to the EA.hy926 cell monolayer at both concentrations. In summary, CLA10,12 showed some pro-inflammatory effects, while CLA9,11 exhibited null or anti-inflammatory effects. The results suggest that each CLA has different effects in ECs under a pro-inflammatory condition, highlighting the need to evaluate the effects of CLA isomers independently.
Text
ijms-1685722_revised_Final
- Accepted Manuscript
More information
Accepted/In Press date: 26 May 2022
e-pub ahead of print date: 29 May 2022
Published date: 1 June 2022
Additional Information:
Funding Information:
Acknowledgments: C.A.V. was supported by CONICYT (Comisión Nacional de Investigación Científica y Tecnológica, Gobierno de Chile) through its scholarship program Becas Chile. E.J.B. was supported by the Biotechnology and Biological Sciences Research Council under the Food Security Doctoral Training Programme and by the Faculty of Medicine, University of Southampton.
Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.
Keywords:
atherosclerosis, conjugated fatty acids, endothelial cells, inflammation
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Local EPrints ID: 457731
URI: http://eprints.soton.ac.uk/id/eprint/457731
ISSN: 1422-0067
PURE UUID: e3f012fa-b476-40cf-8f86-96c6532b2950
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Date deposited: 16 Jun 2022 00:26
Last modified: 17 Mar 2024 03:55
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Author:
Carina Valenzuela
Author:
Ella Baker
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