Up-Regulation of NOD1 and NOD2 through TLR4 and TNF-α in LPS-treated Murine Macrophages

Journal of Veterinary Medical Science

Hiroshi OZAKI⁵  Kazuhiko IMAKAWA³  George M. BAHR¹  Kazuto ISUZUGAWA³  Masateru IIZUKA³  Shinya YAMAMOTO³  Shizuo AKIRA²  Masatoshi HORI⁵  Ei-ichi MOMOTANI⁴  Yasunori MURASE³  Yuji TAKAHASHI³  Misa IMAI³ 

[1] Laboratory of Molecular Immunology of Infection and Inflammation, Institut Pasteur de Lille;Department of Host Defense, Research Institute for Microbial Diseases, Osaka University;Laboratory of Animal Breeding, Graduate School of Agricultural and Life Sciences, The University of Tokyo;National Institute of Animal Health;Laboratory of Veterinary Pharmacology, Graduate School of Agricultural and Life Sciences, The University of Tokyo

关键词: macrophage;    murine;    NOD1;    NOD2;    TNF-α;   

DOI  :  10.1292/jvms.68.471

学科分类：兽医学

来源: Japanese Society of Veterinary Science

【 摘 要 】

References(34)Cited-By(39)NOD1 (Card4) and NOD2 (Card15) are thought to be responsible for cytoplasmic defense against bacterial entry. To gain further knowledge about how their expressions are regulated in murine macrophages, we investigated the expression of NOD1 and NOD2 mRNAs after stimulation with various endotoxins, lipopolysaccharide, lipoteichoic acid and peptidoglycan. In macrophage RAW264.7 cells, the first and second rises in NOD1 and NOD2 mRNAs were observed at 2 hr and at 8-12 hr after endotoxin treatment. Increases in NOD1 and NOD2 mRNAs at 2 hr in lipopolysaccharide-treated RAW264.7 cells were reduced with the use of NF-κB inhibitor, caffeic acid phenetyl ester. In RAW264.7 cells, lipopolysaccharide-induced increases in NOD1 and NOD2 mRNAs were inhibited with anti-TLR4 antibody, and partially reduced in peritoneal macrophages obtained from TLR4-deficient mice. Furthermore, NOD1 and NOD2 mRNA expressions in RAW264.7 cells were increased by the treatment with proinflammatory cytokines, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), or IL-6. In TNF-α deficient macrophages, the expression of NOD molecules was minimal at 12 hr, and the second rise in NOD mRNA seen in lipopolysaccharide-treated RAW264.7 cells was inhibited with anti-TNF-α, but not with anti-IL-1β or anti-IL-6 antibody. These observations suggest that immediate response of NODs to endotoxins could result from NF-κB activation via TLR signaling, whereas the second rise in NOD mRNAs might have resulted from TNF-α production possibly through NF-κB, TLR, and/or NOD signalings.

【 授权许可】

Unknown