In:
Journal of Periodontal Research, Wiley, Vol. 48, No. 6 ( 2013-12), p. 748-756
Abstract:
The interleukin ( IL )‐1 receptor antagonist ( R a) binds to IL ‐1 receptors and inhibits IL ‐1 activity. However, it is unclear whether the IL ‐1 R a plays a protective role in periodontal disease. The purpose of this study was to compare IL ‐1 R a knockout ( KO ) and wild‐type ( WT ) mice in regard to proinflammatory cytokine production, osteoclast formation and bone resorption in response to periodontal bacterial lipopolysaccharide ( LPS ). Material and Methods Peritoneal macrophages ( M φs) were obtained from 13‐wk‐old IL ‐1 R a KO and WT mice. Peritoneal M φs were cultured with or without 10 μg/mL of A ggregatibacter actinomycetemcomitans LPS for 24 h. The levels of IL ‐1alpha ( IL ‐1α), IL ‐1beta ( IL ‐1β), tumor necrosis factor‐α ( TNF ‐α) and IL ‐6 were measured in periotoneal M φs supernatant fluid ( PM‐SF ) using an ELISA . Bone marrow cells were obtained from the mice and stimulated with PM‐SF for 9 d, then stained with TRAP . The frequency of TRAP ‐positive multinucleated giant cell formation was calculated based on a fusion index. PM‐SF ‐stimulated calvarial bone resorption was analyzed using micro‐computed tomography, and calvarial histological analysis was performed using hematoxylin and eosin and TRAP staining. The expression of cyclooxygenase‐2 ( Cox 2 ), prostanoid receptor EP 4 ( Ep4 ) and Rank m RNAs in bone marrow cells were measured using real‐time quantitative PCR , while prostaglandin E 2 ( PGE 2 ) production was determined by ELISA . Results The levels of IL ‐1α, IL ‐1β, TNF ‐α and IL ‐6 in IL ‐1 R a KO mice PM‐SF stimulated with A . actinomycetemcomitans LPS were significantly increased by approximately 4‐ ( p 〈 0.05), 5‐ ( p 〈 0.05), 1.3‐ ( p 〈 0.05) and 6‐ ( p 〈 0.05) fold, respectively, compared with the levels in WT mice. Moreover, osteoclast formation, expression of Rank , Ep 4 and Cox2 m RNAs and production of PGE 2 were significantly increased by approximately 2‐ ( p 〈 0.05), 1.6‐ ( p 〈 0.05), 2.5‐ ( p 〈 0.05), 1.6‐ ( p 〈 0.05) and 1.9‐ ( p 〈 0.05) fold, respectively, in IL ‐1 R a KO mice stimulated with A . actinomycetemcomitans LPS compared with WT mice. Conclusion IL ‐1 R a regulates IL ‐1 activity and appears to reduce the levels of other inflammatory cytokines, including TNF ‐α and IL ‐6, while it also reduces expression of the EP 4 receptor related to prostanoid sensitivity and osteoclast formation. These results suggest that IL ‐1 R a is an important molecule for inhibition of inflammatory periodontal bone resorption.
Type of Medium:
Online Resource
ISSN:
0022-3484
,
1600-0765
DOI:
10.1111/jre.2013.48.issue-6
Language:
English
Publisher:
Wiley
Publication Date:
2013
detail.hit.zdb_id:
2025633-4
Bookmarklink
