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KMID : 0378120030300010009
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Chungnam Medical Journal
2003 Volume.30 No. 1 p.9 ~ p.20
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The Role of Vitamin D_(3) in Nramp1-Mediated Growth Inhibition of Mycobacterium marinum in the Murine Macrophage Line RAW264.7
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Park Jung-Kyu
Jung Saet-Byel
Lee Kil-Soo
Kim Su-Young
Song Chang-Hwa
Park Jong-Ho
Cho Hyun-Koo
Jo Eun-Kyung
Kim Hwa-Jung
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Abstract
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The natural resistance-associated macrophage protein 1(Nramp1) has been proposed to directly regulate bactericidal or bacteriostatic activity of the macrophage toward pathogens or participate in macrophage activation that lead to microbial elimination in the host. The relationship between Nramp1 and nitric oxide(NO) as an antimicrobial factor has not been precisely defined to date. To devise an in vitro assay for Nramp1 function, this study introduced a wild type Nramp1^(G169) cDKA transfected RAW264.7 macrophages(A8) which bear a homozygous mutant Nramp1^(D169) allele and are permissive to replication of specific intracellular parasites.
RAW264.7 and A8 macrophages did not produce NO, but vitamin D_(3)-activated-Mycobacterium marinum-infected RAW264.7 and A8 macrophages pretreated with vitamin D_(3) leaded to the increase of NO production and growth inhibition of M. marinum. Inhibition of NO production by a NO inhibitor, L-NAME, abolished the above effects. The mRNA expression of iNOS in infected macrophages with costimulated vitamin D_(3) was increased. IFN-γ activated macrophages also showed the same results with vitamin D_(3) activated macrophages.
These results suggest that bactericidal or bacteriostatic activity in RAW264.7 and A8 macrophages correlated with the production of NO, although NO might not be the only factor responsible for controlling M. marinum infection. The Nrampl gene is considered to be a cofactor in the controlling the replication of M. marinum infection.
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KEYWORD
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Nramp1, M. marinum, Vitamin D_(3), Nitric oxide
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