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Journal of Endotoxin Research, Vol. 9, No. 2, 85-90 (2003)
DOI: 10.1177/09680519030090020201
© 2003 SAGE Publications

C 2-ceramide inhibits LPS-induced nitric oxide production in RAW 264.7 macrophage cells through down-regulating the activation of Akt

Naoki Koide

Department of Microbiology and Immunology and Division of Bacterial Toxin, Research Center for Infectious Disease, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan

Tsuyoshi Sugiyama

Department of Microbiology and Immunology and Division of Bacterial Toxin, Research Center for Infectious Disease, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan

Isamu Mori

Department of Microbiology and Immunology and Division of Bacterial Toxin, Research Center for Infectious Disease, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan

Mya Mya Mu

Department of Microbiology and Immunology and Division of Bacterial Toxin, Research Center for Infectious Disease, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan

Tomoaki Yoshida

Department of Microbiology and Immunology and Division of Bacterial Toxin, Research Center for Infectious Disease, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan

Takashi Yokochi

Department of Microbiology and Immunology and Division of Bacterial Toxin, Research Center for Infectious Disease, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan, yokochi{at}aichi-med-u.ac.jp

The effect of C2-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 C2-ceramide inhibited LPS-induced NO production. It was due to the attenuated expression of the inducible type of NO synthase (iNOS). C2-ceramide did not influence the phosphorylation of a series of mitogen-activated protein (MAP) kinases in response to LPS. On the other hand, C2-ceramide down-regulated the phosphorylation of Akt in LPS-stimulated RAW 264.7 cells, followed by the impairment of nuclear factor (NF)-{kappa}B activation. Moreover, the Akt dominant-negative mutant inhibited LPS-induced NO production. C2-ceramide was suggested to inhibit LPS-induced NO production through down-regulating the activation of Akt.


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