Green tea polyphenol inhibits Mycobacterium tuberculosis survival within human macrophages.
Lack of maturation of phagosomes containing pathogenic Mycobacterium tuberculosis within macrophages has been widely recognized as a crucial factor for the persistence of mycobacterial pathogen. Host molecule tryptophan-aspartate containing coat protein (TACO) has been shown to play a crucial role in the arrest of such a maturation process. The present study was addressed to understand whether or not polyphenols derived from green tea could down-regulate TACO gene transcription. And if yes, what impact TACO gene down-regulation has on the uptake/survival of M. tuberculosis within macrophages. The reverse-transcriptase polymerase chain reaction and reporter assay technology, employed in this study, revealed that the major component of green tea polyphenols, epigallocatechin-3-gallate had the inherent capacity to down-regulate TACO gene transcription within human macrophages through its ability to inhibit Sp1 transcription factor. We also found out that TACO gene promoter does contain Sp1 binding sequence using bioinformatics tools. The down-regulation of TACO gene expression by epigallocatechin-3-gallate was accompanied by inhibition of mycobacterium survival within macrophages as assessed through flow cytometry and colony counts. Based on these results, we propose that epigallocatechin-3-gallate may be of importance in the prevention of tuberculosis infection.
Anand
Paras K
PK
Molecular Biology Unit, Department of Experimental Medicine and Biotechnology, Chandigarh 160 012, India.
Kaul
Deepak
D
Sharma
Meera
M
D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D028241:Camellia sinensis / Q000737:chemistry; D002392:Catechin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D015169:Colony Count, Microbial; D015536:Down-Regulation / Q000187:drug effects; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D019169:Jurkat Cells; D008264:Macrophages / Q000378:metabolism* / Q000382:microbiology; D008840:Microfilament Proteins / Q000096:biosynthesis; D009169:Mycobacterium tuberculosis / Q000254:growth & development*; D010636:Phenols / Q000737:chemistry / Q000494:pharmacology; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D059808:Polyphenols; D016329:Sp1 Transcription Factor / Q000037:antagonists & inhibitors / Q000378:metabolism; D014376:Tuberculosis / Q000517:prevention & control
D000975:Antioxidants; D005419:Flavonoids; D008840:Microfilament Proteins; D010636:Phenols; D010936:Plant Extracts; D059808:Polyphenols; D016329:Sp1 Transcription Factor; C072061:coronin proteins; D002392:Catechin; C045651:epigallocatechin gallate