title: The immunomodulatory activity of secondary metabolites isolated from Streptomyces calvus on human peripheral blood mononuclear cells.
abstract: BACKGROUND
  The natural products derived from micro-organisms are potential candidates for the discovery of novel drugs. Streptomyces bacteria are prolific sources of secondary metabolites with a wide variety of biological activities. Streptomyces calvus (S. calvus) is one strain of this genus and may be an appropriate candidate for isolating new compounds. In this study, the immunomodulatory effects of S. calvus secondary metabolites on the expression of various cytokine genes by human peripheral blood mononuclear cells (PBMCs) were evaluated.
  
  
  METHODS
  A bacterial sample was inoculated in Mueller Hinton Broth and secondary metabolites were extracted. PBMCs were isolated from venous blood and were treated with S. calvus secondary metabolites for 48 h. The cell proliferation was assessed by Methyl tetrazolium bromide (MTT) assay and quantitative real-time polymerase chain reaction (qRT-PCR) assays to survey mRNA expressions of selected pro-inflammatory and inhibitory cytokine genes.
  
  
  RESULTS
  Secondary metabolites augmented interleukin-2 and interferon-γ gene expression in PBMCs at low doses and also reduced the levels of immunosuppressive cytokine interleukin-10. In addition, the proliferation of PBMCs substantially increased in response to metabolite treatment in a concentration-dependent manner (p < 0.001).
  
  
  CONCLUSIONS
  This in vitro study revealed that the secondary metabolites from S. calvus can successfully stimulate human PBMCs. Therefore, these metabolites have the potential to serve as robust immunomodulators.
authors.affiliation: a Immunology Research Center , Tabriz University of Medical Sciences , Tabriz , Iran.
authors.forename: Fariba
authors.initials: F
authors.lastname: Mahmoudi
authors.affiliation: a Immunology Research Center , Tabriz University of Medical Sciences , Tabriz , Iran.
authors.forename: Behzad
authors.initials: B
authors.lastname: Baradaran
authors.affiliation: b Biotechnology Department , East Azerbaijan Research and Education Center Agricultural and Natural Resources, AREEO , Tabriz , Iran.|c Department of Biological Sciences , Higher Education Institute of Rab-Rashid , Tabriz , Iran.
authors.forename: Alireza
authors.initials: A
authors.lastname: Dehnad
authors.affiliation: a Immunology Research Center , Tabriz University of Medical Sciences , Tabriz , Iran.
authors.forename: Dariush
authors.initials: D
authors.lastname: Shanehbandi
authors.affiliation: a Immunology Research Center , Tabriz University of Medical Sciences , Tabriz , Iran.
authors.forename: Leila
authors.initials: L
authors.lastname: Mohamed Khosroshahi
authors.affiliation: a Immunology Research Center , Tabriz University of Medical Sciences , Tabriz , Iran.|d Faculty of Veterinary Medicine, Department of Pathobiology , University of Tabriz , Tabriz , Iran.
authors.forename: Mahyar
authors.initials: M
authors.lastname: Aghapour
mesh_terms: D049109:Cell Proliferation / Q000187:drug effects*; D006801:Humans; D007155:Immunologic Factors / Q000096:biosynthesis*; D066298:In Vitro Techniques; D007963:Leukocytes, Mononuclear / Q000187:drug effects*; D060888:Real-Time Polymerase Chain Reaction; D013302:Streptomyces / Q000378:metabolism*
chemical_list: D007155:Immunologic Factors
keywords: Human peripheral blood mononuclear cells; Streptomyces calvus; immunomodulation; interferon-γ; interleukin-10; interleukin-2