title: Human beta casein fragment (54-59) modulates M. bovis BCG survival and basic transcription factor 3 (BTF3) expression in THP-1 cell line.
abstract: Immunostimulatory peptides potentiate the immune system of the host and are being used as a viable adjunct to established therapeutic modalities in treatment of cancer and microbial infections. Several peptides derived from milk protein have been reported to induce immunostimulatory activity. Human β -casein fragment (54-59), natural sequence peptide (NS) carrying the Val-Glu-Pro-Ile-Pro-Tyr amino acid residues, was reported to activate the macrophages and impart potent immunostimulatory activity. In present study, we found that this peptide increases the clearance of M. bovis BCG from THP-1 cell line in vitro. The key biomolecules, involved in the clearance of BCG from macrophage like, nitric oxide, pro-inflammatory cytokines and chemokines, were not found to be significantly altered after peptide treatment in comparison to the untreated control. Using proteomic approach we found that BTF3a, an isoform of the Basic Transcription Factor, BTF3, was down regulated in THP-1 cell line after peptide treatment. This was reconfirmed by real time RT-PCR and western blotting. We report the BTF3a as a novel target of this hexapeptide. Based on the earlier findings and the results from the present studies, we suggest that the down regulation of BTF3a following the peptide treatment may augment the M. bovis BCG mediated apoptosis resulting in enhanced clearance of M. bovis BCG from THP-1 cell line.
authors.affiliation: Division of Toxicology, Central Drug Research Institute, Lucknow, India.
authors.forename: Dharamsheela
authors.initials: D
authors.lastname: Thakur
authors.forename: Reshu
authors.initials: R
authors.lastname: Saxena
authors.forename: Vandana
authors.initials: V
authors.lastname: Singh
authors.forename: Wahajul
authors.initials: W
authors.lastname: Haq
authors.forename: S B
authors.initials: SB
authors.lastname: Katti
authors.forename: Bhupendra Narain
authors.initials: BN
authors.lastname: Singh
authors.forename: Raj Kamal
authors.initials: RK
authors.lastname: Tripathi
mesh_terms: D000595:Amino Acid Sequence; D000904:Antibiotics, Antitubercular / Q000494:pharmacology*; D017209:Apoptosis; D002364:Caseins / Q000494:pharmacology*; D002460:Cell Line; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D054884:Host-Pathogen Interactions / Q000187:drug effects; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects; D050296:Microbial Viability / Q000187:drug effects*; D008969:Molecular Sequence Data; D009163:Mycobacterium bovis / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D020543:Proteome / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D000904:Antibiotics, Antitubercular; D002364:Caseins; D018925:Chemokines; D016207:Cytokines; D007155:Immunologic Factors; D008070:Lipopolysaccharides; D009687:Nuclear Proteins; D010446:Peptide Fragments; D020033:Protein Isoforms; D020543:Proteome; D014157:Transcription Factors; C063552:transcription factor BTF3; D009569:Nitric Oxide