C2-ceramide inhibits LPS-induced nitric oxide production in RAW 264.7 macrophage cells through down-regulating the activation of Akt

Department of Microbiology and Immunology and Division of Bacterial Toxin, Research Center for Infectious Disease, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan.
Journal of Endotoxin Research (Impact Factor: 3.06). 02/2003; 9(2):85-90. DOI: 10.1179/096805103125001450
Source: PubMed


The effect of C(2)-ceramide, a membrane-permeable ceramide analogue, on nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells was studied. The non-toxic concentration of C(2)-ceramide inhibited LPS-induced NO production. It was due to the attenuated expression of the inducible type of NO synthase (iNOS). C(2)-ceramide did not influence the phosphorylation of a series of mitogen-activated protein (MAP) kinases in response to LPS. On the other hand, C(2)-ceramide down-regulated the phosphorylation of Akt in LPS-stimulated RAW 264.7 cells, followed by the impairment of nuclear factor (NF)-kappaB activation. Moreover, the Akt dominant-negative mutant inhibited LPS-induced NO production. C(2)-ceramide was suggested to inhibit LPS-induced NO production through down-regulating the activation of Akt.

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