title: Salmeterol, a Long-Acting β2-Adrenergic Receptor Agonist, Inhibits Macrophage Activation by Lipopolysaccharide From Porphyromonas gingivalis.
abstract: Salmeterol is a long-acting β2-adrenergic receptor agonist used to treat chronic obstructive pulmonary disease. The authors of the current study previously showed that preincubation of primary microglial-enriched cells with salmeterol could inhibit the inflammatory response induced by Escherichia coli lipopolysaccharide (LPS), a Toll-like receptor (TLR)-4 agonist. In this study, the authors sought to determine if salmeterol had a similar inhibitory effect on the inflammatory response of the murine macrophage cell line RAW264.7 and human monocyte THP-1 to LPS from Porphyromonas gingivalis (PgLPS), an oral microbe implicated in the pathogenesis of periodontal disease.
  
  
  
  RAW264.7 and THP-1 cells were pretreated with salmeterol, followed by PgLPS, and monitored for production of inflammatory mediators by enzyme-linked immunosorbent assay. The nitric oxide concentration and nuclear factor-kappa B (NF-κB) activity were measured by Griess method and secretory alkaline phosphatase reporter activity assay, respectively. Reverse-transcriptase polymerase chain reaction and immunoblot analysis were used to measure messenger RNA and protein levels. Nuclear translocation of NF-κB was detected by immunofluorescence.
  
  
  
  Pretreatment with salmeterol significantly inhibited production of proinflammatory mediators by RAW264.7 and THP-1 cells. Salmeterol downregulated PgLPS-mediated phosphorylation of the extracellular signal-regulated kinase 1/2 and c-Jun N-terminal kinase but not p38 mitogen-activated protein kinases (MAPKs). Salmeterol also attenuated activation of NF-κB via inhibition of nuclear translocation of p65-NFκB, the transcriptional activity of NF-κB and IκBα phosphorylation.
  
  
  
  Salmeterol can significantly inhibit activation of macrophage-mediated inflammation by PgLPS, suggesting that use of salmeterol may be an effective treatment in inhibiting or lessening the inflammatory response mediated through TLR pathway activation.
authors.affiliation: Department of Dentistry, Faculty of Medicine and Dentistry, Katz Group Center for Pharmacy and Health Research, University of Alberta, Edmonton, Alberta.
authors.forename: Monika
authors.initials: M
authors.lastname: Sharma
authors.affiliation: Department of Dentistry, Faculty of Medicine and Dentistry, Katz Group Center for Pharmacy and Health Research, University of Alberta, Edmonton, Alberta.
authors.forename: Lindsay
authors.initials: L
authors.lastname: Patterson
authors.affiliation: Department of Dentistry, Faculty of Medicine and Dentistry, Katz Group Center for Pharmacy and Health Research, University of Alberta, Edmonton, Alberta.
authors.forename: Elisha
authors.initials: E
authors.lastname: Chapman
authors.affiliation: Department of Dentistry, Faculty of Medicine and Dentistry, Katz Group Center for Pharmacy and Health Research, University of Alberta, Edmonton, Alberta.
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Flood
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects*; D051379:Mice; D000072000:NF-KappaB Inhibitor alpha / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D016966:Porphyromonas gingivalis; D000067996:RAW 264.7 Cells; D000068299:Salmeterol Xinafoate / Q000494:pharmacology* / Q000627:therapeutic use; D000074084:THP-1 Cells; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D008070:Lipopolysaccharides; D016328:NF-kappa B; D000072000:NF-KappaB Inhibitor alpha; D000068299:Salmeterol Xinafoate; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Cytokines; NF-kappa B; Toll-like receptors; monocytes; nitric oxide; periodontitis