Article ; Online: A novel fatty acid analogue triggers CD36-GPR120 interaction and exerts anti-inflammatory action in endotoxemia.
Cellular and molecular life sciences : CMLS
2024 Volume 81, Issue 1, Page(s) 176
Abstract: 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-1β, IL- ...
Abstract | 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-1β, IL-6 and TNF-α) 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-1β, IL-6 and TNF-α) 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-1β, IL-6 and TNF-α 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. |
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MeSH term(s) | Animals ; Mice ; Endotoxemia/chemically induced ; Interleukin-6/genetics ; Lipopolysaccharides/toxicity ; Tumor Necrosis Factor-alpha ; Anti-Inflammatory Agents/pharmacology ; Anti-Inflammatory Agents/therapeutic use ; Inflammation ; CD36 Antigens/genetics ; Cytokines/genetics ; Interleukin-1beta/genetics ; RNA, Messenger ; Fatty Acids |
Chemical Substances | Interleukin-6 ; Lipopolysaccharides ; Tumor Necrosis Factor-alpha ; Anti-Inflammatory Agents ; CD36 Antigens ; Cytokines ; Interleukin-1beta ; RNA, Messenger ; Fatty Acids |
Language | English |
Publishing date | 2024-04-10 |
Publishing country | Switzerland |
Document type | Journal Article |
ZDB-ID | 1358415-7 |
ISSN | 1420-9071 ; 1420-682X |
ISSN (online) | 1420-9071 |
ISSN | 1420-682X |
DOI | 10.1007/s00018-024-05207-1 |
Database | MEDical Literature Analysis and Retrieval System OnLINE |
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