Abstract
The present study was conducted to see the role of NF-kappaB in virulent (Mycobacterium tuberculosis H37Rv) and avirulent (M. tuberculosis H37Ra) mycobacterial infection in THP-1 cells. To inactivate NF-kappaB, pCMV-IkappaBalphaM dn containing THP-1 cell line was generated which showed marked increase in apoptosis with M. tuberculosis H37Rv and M. tuberculosis H37Ra. Infected THP-1-IkappaBalphaM dn cells showed decrease in mitochondrial membrane potential, cytochrome c release, activation of caspase-3 and enhanced TNF-alpha production. Increase in apoptosis of infected THP-1-IkappaBalphaM dn cells resulted in inhibition of intracellular mycobacterial growth. Differential NF-kappaB activation potential was observed with M. tuberculosis H37Rv and M. tuberculosis H37Ra. Both the strains activated NF-kappaB after 4 h in THP-1 cells however after 48 h only M. tuberculosis H37Rv activated NF-kappaB which lead to up-regulation of bcl-2 family anti-apoptotic member, bfl-1/A1. Our results indicated that NF-kappaB activation may be a determinant factor for the success of virulent mycobacteria within macrophages.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis*
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Caspase 3 / metabolism
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Cell Line
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Cytochromes c / metabolism
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Enzyme Activation
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Humans
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I-kappa B Proteins / genetics
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I-kappa B Proteins / metabolism
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Macrophages / metabolism*
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Macrophages / microbiology
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Membrane Potential, Mitochondrial
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Microbial Viability
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Minor Histocompatibility Antigens
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Mitochondria / metabolism
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Mitochondria / microbiology
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Mutation
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Mycobacterium tuberculosis / growth & development
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Mycobacterium tuberculosis / isolation & purification*
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Mycobacterium tuberculosis / pathogenicity
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NF-KappaB Inhibitor alpha
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NF-kappa B / metabolism*
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Protein Transport
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Proto-Oncogene Proteins c-bcl-2 / biosynthesis
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RNA, Messenger / biosynthesis
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Time Factors
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Transcription Factor RelA / metabolism
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Transfection
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Tuberculosis / metabolism*
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Tuberculosis / microbiology
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Tuberculosis / physiopathology
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Tumor Necrosis Factor-alpha / biosynthesis
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Up-Regulation
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Virulence
Substances
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BCL2-related protein A1
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I-kappa B Proteins
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Minor Histocompatibility Antigens
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NF-kappa B
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NFKBIA protein, human
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Proto-Oncogene Proteins c-bcl-2
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RNA, Messenger
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Transcription Factor RelA
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Tumor Necrosis Factor-alpha
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NF-KappaB Inhibitor alpha
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Cytochromes c
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Caspase 3