Differential expression of NF-kappaB in mycobacteria infected THP-1 affects apoptosis.
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.
Dhiman
Rohan
R
Division of Cell Biology and Immunology, Institute of Microbial Technology (CSIR), Chandigarh 160 036, India.
Raje
Manoj
M
Majumdar
Sekhar
S
D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D045304:Cytochromes c / Q000378:metabolism; D004789:Enzyme Activation; D006801:Humans; D020672:I-kappa B Proteins / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism* / Q000382:microbiology; D053078:Membrane Potential, Mitochondrial; D050296:Microbial Viability; D015778:Minor Histocompatibility Antigens; D008928:Mitochondria / Q000378:metabolism / Q000382:microbiology; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000254:growth & development / Q000302:isolation & purification* / Q000472:pathogenicity; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D021381:Protein Transport; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D013997:Time Factors; D051996:Transcription Factor RelA / Q000378:metabolism; D014162:Transfection; D014376:Tuberculosis / Q000378:metabolism* / Q000382:microbiology / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D015854:Up-Regulation; D014774:Virulence
C096816:BCL2-related protein A1; D020672:I-kappa B Proteins; D015778:Minor Histocompatibility Antigens; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha; D045304:Cytochromes c; D053148:Caspase 3