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.
Highlights
Peptide therapy is being increasingly used in clinical applications and certain naturally derived peptides have been successfully used for many years [1]
We found that the natural sequence peptide (NS) peptide decreased the survival of M. bovis BCG in THP-1 cell line in a dose dependent manner
Since NS peptide reportedly exert its immunostimulatory activity through macrophage activation, the peptide mediated macrophage activation may lead to increased clearance of M. bovis BCG, as tubercle bacilli reside mainly within host macrophages and the activation of macrophages determines the survival of bacilli inside macrophage [8]
Summary
Peptide therapy is being increasingly used in clinical applications and certain naturally derived peptides have been successfully used for many years [1]. The successful usage of many peptides with known immunostimulatory properties as a viable adjunct to established therapeutic modalities allows the emergence of a novel approach for the treatment of infectious and malignant conditions in coming decades. Since the discovery of muramyl dipeptide (MDP), the smallest fragment of bacterial peptidoglycan carrying immunostimulatory activity in 1974 [2,3,4], efforts were on to develop chemically defined low molecular weight substances as immunostimulating agents. Novel chemically well-defined and clinically acceptable immune modulators and several glycopeptides and lipopeptides with close structural resemblance to MDP have been designed and synthesized. Most of them have microbial origin and are associated with some toxic side effects
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