A novel fatty acid analogue triggers CD36-GPR120 interaction and exerts anti-inflammatory action in endotoxemia

0585609 - ÚOCHB 2025 RIV CH eng J - Článek v odborném periodiku
Boutanquoi, P. M. - Khan, A. S. - Cabeza, L. - Jantzen, L. - Gautier, T. - Yesylevskyy, Semen - Ramseyer, C. - Masson, D. - Van Waes, V. - Hichami, A. - Khan, N. A.
A novel fatty acid analogue triggers CD36-GPR120 interaction and exerts anti-inflammatory action in endotoxemia.
Cellular and Molecular Life Sciences. Roč. 81, č. 1 (2024), č. článku 176. ISSN 1420-682X. E-ISSN 1420-9071
Institucionální podpora: RVO:61388963
Klíčová slova: fat * lipids * lipopolysaccharide * taste buds * inflammation
Impakt faktor: 8, rok: 2022
Způsob publikování: Open access
https://doi.org/10.1007/s00018-024-05207-1

Inflammation is a mediator of a number of chronic pathologies. We synthesized the diethyl (9Z,12Z)-octadeca-9,12-dien-1-ylphosphonate, called NKS3, which decreased lipopolysaccharide (LPS)-induced mRNA upregulation of proinflammatory cytokines (IL-1 beta, IL-6 and TNF-alpha) not only in primary intraperitoneal and lung alveolar macrophages, but also in freshly isolated mice lung slices. The in-silico studies suggested that NKS3, being CD36 agonist, will bind to GPR120. Co-immunoprecipitation and proximity ligation assays demonstrated that NKS3 induced protein-protein interaction of CD36 with GPR120in RAW 264.7 macrophage cell line. Furthermore, NKS3, via GPR120, decreased LPS-induced activation of TAB1/TAK1/JNK pathway and the LPS-induced mRNA expression of inflammatory markers in RAW 264.7 cells. In the acute lung injury model, NKS3 decreased lung fibrosis and inflammatory cytokines (IL-1 beta, IL-6 and TNF-alpha) and nitric oxide (NO) production in broncho-alveolar lavage fluid. NKS3 exerted a protective effect on LPS-induced remodeling of kidney and liver, and reduced circulating IL-1 beta, IL-6 and TNF-alpha concentrations. In a septic shock model, NKS3 gavage decreased significantly the LPS-induced mortality in mice. In the last, NKS3 decreased neuroinflammation in diet-induced obese mice. Altogether, these results suggest that NKS3 is a novel anti-inflammatory agent that could be used, in the future, for the treatment of inflammation-associated pathologies.
Trvalý link: https://hdl.handle.net/11104/0353283