title: Rhodomyrtone modulates innate immune responses of THP-1 monocytes to assist in clearing methicillin-resistant Staphylococcus aureus.
abstract: BACKGROUND
  The increasing resistance of Staphylococcus aureus to conventional antibiotics poses a major health problem. Moreover, S. aureus can survive within phagocytes, thus evading some antibiotics and the innate immune response. Rhodomyrtone, a bioactive compound from the leaves of Rhodomyrtus tomentosa, possesses potent antibacterial activity against methicillin-resistant S. aureus (MRSA). This study was to investigate the immunomodulatory effects of rhodomyrtone on THP-1 monocytes in response to MRSA.
  
  
  METHODS
  THP-1 monocytes were stimulated with heat-killed MRSA, followed by treatment with rhodomyrtone. The cell pellets were prepared to detect pro-inflammatory molecules using real-time PCR. The supernatants were collected to assess nitric oxide production using Griess assay. Assays for phagocytosis and bacterial killing by THP-1 monocytes were performed to determine if they were affected by rhodomyrtone.
  
  
  RESULTS
  Expression of pro-inflammatory molecules including IL-1β, TNF-α, IL-6, and iNOS was enhanced in THP-1 monocytes stimulated with high doses of heat-killed MRSA (108 to 109 cfu/ml). In contrast, monocytes stimulated with MRSA at lower doses (106 to 107 cfu/ml) did not induce the expression of these cytokines. However, rhodomyrtone significantly increased the expression of pro-inflammatory mediators, IL-6 and iNOS in monocytes stimulated with heat-killed MRSA at low doses, and displayed some anti-inflammatory activity by reducing TNF-α expression in monocytes stimulated with heat-killed MRSA at high doses. Treatment with rhodomyrtone also significantly up-regulated the expression of the key pattern recognition receptors, TLR2 and CD14, in THP-1 monocytes stimulated with heat-killed MRSA at 106 to 109 cfu/ml, while heat-killed MRSA alone did not induce the expression of these molecules. The ability of rhodomyrtone to eliminate MRSA from the monocytes was observed within 24 h after treatment.
  
  
  CONCLUSIONS
  Rhodomyrtone enhanced the expression of pattern recognition receptors by monocytes in response to MRSA. Increased expression of these receptors might improve MRSA clearance by modulating pro- and anti-inflammatory cytokine responses.
authors.affiliation: Department of Microbiology and Natural Products Research Center of Excellence, Faculty of Science, Prince of Songkla University, Songkla, Thailand.
authors.forename: Sutthirat
authors.initials: S
authors.lastname: Srisuwan
authors.affiliation: Graduate Program in Biomedical Sciences, Faculty of Allied Health Sciences, Thammasat University, Pathumtanee, Thailand.
authors.forename: Pongsri
authors.initials: P
authors.lastname: Tongtawe
authors.affiliation: Graduate Program in Biomedical Sciences, Faculty of Allied Health Sciences, Thammasat University, Pathumtanee, Thailand.
authors.forename: Potjanee
authors.initials: P
authors.lastname: Srimanote
authors.affiliation: Department of Microbiology and Natural Products Research Center of Excellence, Faculty of Science, Prince of Songkla University, Songkla, Thailand.
authors.forename: Supayang Piyawan
authors.initials: SP
authors.lastname: Voravuthikunchai
mesh_terms: D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects*; D042541:Intracellular Space / Q000187:drug effects / Q000382:microbiology; D018950:Lipopolysaccharide Receptors / Q000235:genetics / Q000378:metabolism; D055624:Methicillin-Resistant Staphylococcus aureus / Q000502:physiology*; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D010587:Phagocytosis / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000235:genetics; D044004:Xanthones / Q000494:pharmacology*
chemical_list: D016207:Cytokines; D018950:Lipopolysaccharide Receptors; D012333:RNA, Messenger; D051195:Toll-Like Receptor 2; D044004:Xanthones; C541823:rhodomyrtone; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II