Human beta casein fragment (54-59) modulates M. bovis BCG survival and basic transcription factor 3 (BTF3) expression in THP-1 cell line

Dharamsheela Thakur; Reshu Saxena; Vandana Singh; Wahajul Haq; S B Katti; Bhupendra Narain Singh; Raj Kamal Tripathi

doi:10.1371/journal.pone.0045905

Human beta casein fragment (54-59) modulates M. bovis BCG survival and basic transcription factor 3 (BTF3) expression in THP-1 cell line

PLoS One. 2012;7(9):e45905. doi: 10.1371/journal.pone.0045905. Epub 2012 Sep 28.

Authors

Dharamsheela Thakur¹, Reshu Saxena, Vandana Singh, Wahajul Haq, S B Katti, Bhupendra Narain Singh, Raj Kamal Tripathi

Affiliation

¹ Division of Toxicology, Central Drug Research Institute, Lucknow, India.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Antibiotics, Antitubercular / pharmacology*
Apoptosis
Caseins / pharmacology*
Cell Line
Chemokines / genetics
Chemokines / metabolism
Cytokines / genetics
Cytokines / metabolism
Down-Regulation / drug effects
Gene Expression / drug effects
Host-Pathogen Interactions / drug effects
Humans
Immunologic Factors / pharmacology
Lipopolysaccharides / pharmacology
Macrophage Activation / drug effects
Microbial Viability / drug effects*
Molecular Sequence Data
Mycobacterium bovis / drug effects
Mycobacterium bovis / physiology*
Nitric Oxide / metabolism
Nuclear Proteins / genetics
Nuclear Proteins / metabolism*
Peptide Fragments / pharmacology*
Protein Isoforms / genetics
Protein Isoforms / metabolism
Proteome / genetics
Proteome / metabolism
Transcription Factors / genetics
Transcription Factors / metabolism*

Substances

Antibiotics, Antitubercular
Caseins
Chemokines
Cytokines
Immunologic Factors
Lipopolysaccharides
Nuclear Proteins
Peptide Fragments
Protein Isoforms
Proteome
Transcription Factors
transcription factor BTF3
Nitric Oxide

Grants and funding

We are thankful to the “Council of Scientific and Indistrial Research (CSIR)- Central Drug Research Institute (CDRI)” for providing the institutional funding and Alternative Animal Model project (NWP0034) for providing the financial support. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.