Effect of nifedipine, a calcium channel blocker, on the generation of nitric oxide and interleukin-1β by murine macrophages activated by lipopolysaccharide from Prevotella intermedia.
Animals
Calcium Channel Blockers
/ pharmacology
Interleukin-1beta
/ metabolism
Lipopolysaccharides
/ pharmacology
Mice
NF-kappa B
/ metabolism
Nifedipine
/ pharmacology
Nitric Oxide
/ metabolism
Prevotella intermedia
RAW 264.7 Cells
STAT1 Transcription Factor
/ metabolism
STAT3 Transcription Factor
/ metabolism
Interleukin-1β
Lipopolysaccharide
Nifedipine
Nitric oxide
Periodontal disease
Journal
Naunyn-Schmiedeberg's archives of pharmacology
ISSN: 1432-1912
Titre abrégé: Naunyn Schmiedebergs Arch Pharmacol
Pays: Germany
ID NLM: 0326264
Informations de publication
Date de publication:
01 2021
01 2021
Historique:
received:
13
04
2020
accepted:
03
08
2020
pubmed:
12
8
2020
medline:
21
10
2021
entrez:
12
8
2020
Statut:
ppublish
Résumé
Nifedipine, a calcium channel blocker, has been reported to possess anti-inflammatory and immunosuppressive effects. The current study was undertaken to explore the influence of nifedipine on the generation of proinflammatory mediators by murine macrophages activated by lipopolysaccharide (LPS) prepared from Prevotella intermedia, a putative periodontal pathogen, and associated mechanisms of action as well. LPS was purified by employing phenol-water extraction protocol. Culture supernatants were analyzed for nitric oxide (NO) and interleukin (IL)-1β. Real-time PCR and immunoblotting were conducted to quantify mRNA and protein expression, respectively. NF-κB-dependent secreted embryonic alkaline phosphatase (SEAP) levels were estimated by reporter assay. Nifedipine markedly suppressed the generation of iNOS-derived NO and IL-1β together with their mRNA expressions in murine macrophages activated by P. intermedia LPS. LPS-stimulated cells exposed to nifedipine notably increased the mRNA levels of Arg-1, Ym-1, FIZZ1, and TGF-β, which are typical markers for M2 macrophage polarization. Nifedipine induced HO-1 at both gene and protein levels in cells challenged with P. intermedia LPS, and the nifedipine-mediated inhibition of NO generation was significantly abrogated by adding SnPP, an HO-1 inhibitor. Nifedipine inhibited LPS-evoked generation of NO and IL-1β in a PPAR-γ-independent manner. In addition, NF-κB activation as well as phosphorylation of STAT1/3 induced by P. intermedia LPS was suppressed by nifedipine. Nifedipine is an inhibitor of P. intermedia LPS-evoked production of NO and IL-1β in murine macrophages and encourages macrophage polarization toward the M2 phenotype. Nifedipine possibly has potential to be used for host modulation of periodontal disease and is worth being further researched.
Identifiants
pubmed: 32780228
doi: 10.1007/s00210-020-01958-3
pii: 10.1007/s00210-020-01958-3
doi:
Substances chimiques
Calcium Channel Blockers
0
IL1B protein, mouse
0
Interleukin-1beta
0
Lipopolysaccharides
0
NF-kappa B
0
STAT1 Transcription Factor
0
STAT3 Transcription Factor
0
Stat1 protein, mouse
0
Stat3 protein, mouse
0
Nitric Oxide
31C4KY9ESH
Nifedipine
I9ZF7L6G2L
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
59-71Références
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