Details

Autor(en) / Beteiligte

• Sharma, Monika
• Patterson, Lindsay
• Chapman, Elisha
• Flood, Patrick M.

Titel

Salmeterol, a Long‐Acting β2‐Adrenergic Receptor Agonist, Inhibits Macrophage Activation by Lipopolysaccharide From Porphyromonas gingivalis

Ist Teil von

• Journal of periodontology (1970), 2017-07, Vol.88 (7), p.681-692

Ort / Verlag

United States: American Academy of Periodontology

Erscheinungsjahr

2017

Quelle

Wiley Online Library All Journals

Beschreibungen/Notizen

• Background: 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. Methods: 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. Results: 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. Conclusion: 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.