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This article reports an inhibitory effect of rapamycin on the lipopolysac-charide (LPS)-induced expression of both inducible nitric oxide synthase (iNOS) and granulocyte-colony stimulating factor (G-CSF) in macrophages and its underlying mechanism. | IFEBS Journal Rapamycin inhibits lipopolysaccharide induction of granulocyte-colony stimulating factor and inducible nitric oxide synthase expression in macrophages by reducing the levels of octamer-binding factor-2 Yuan-Yi Chou1 Jhen-I Gao1 Shwu-Fen Chang2 Po-Yuan Chang3 and Shao-Chun Lu1 1 Department of Biochemistry and Molecular Biology College of Medicine NationalTaiwan University Taipei Taiwan 2 Graduate Institute of MedicalSciences Taipei MedicalUniversity Taiwan 3 Department of InternalMedicine NationalTaiwan University Hospital NationalTaiwan University Taipei Taiwan Keywords granulocyte-colony stimulating factor G-CSF inducible nitric oxide synthase iNOS lipopolysaccharide LPS macrophage mammalian target of rapamycin mTOR octamer-binding factor-2 Oct-2 rapamycin Correspondence S.-C. Lu Room 810 No.1 Jen Ai Road Section 1 Department of Biochemistry and Molecular Biology College of Medicine NationalTaiwan University Taipei 10051 Taiwan Tel 886 2 2312 3456 ext. 88224 Fax 886 2 2391 5295 E-mail lsc@ntu.edu.tw Website http www.mc.ntu.edu.tw department ibmb Received 22 July 2010 revised 5 October 2010 accepted 21 October 2010 doi 10.1111 j.1742-4658.2010.07929.x This article reports an inhibitory effect of rapamycin on the lipopolysaccharide LPS -induced expression of both inducible nitric oxide synthase iNOS and granulocyte-colony stimulating factor G-CSF in macrophages and its underlying mechanism. The study arose from an observation that rapamycin inhibited the LPS-induced increase in octamer-binding factor-2 Oct-2 protein levels through a mammalian target of rapamycin mTOR -dependent pathway in mouse RAW264.7 macrophages. As both iNOS and G-CSF are potential Oct-2 target genes we tested the effect of rapamycin on their expression and found that it reduced the LPS-induced increase in iNOS and G-CSF mRNA levels and iNOS and G-CSF protein levels. Blocking of mTOR-signaling using a dominant-negative mTOR expression plasmid resulted in inhibition of the .
