title: IL-17 receptor A signaling is protective in infection-stimulated periapical bone destruction.
abstract: IL-17 is a pleiotropic cytokine produced by Th17 T cells that induces a myriad of proinflammatory mediators. However, different models of inflammation report opposite functional roles of IL-17 signal in terms of its effects on bone destruction. In this study we determined the role of IL-17RA signal in bone resorption stimulated by dentoalveolar infections. Infrabony resorptive lesions were induced by surgical pulp exposure and microbial infection of mouse molar teeth. IL-17 was strongly induced in periapical tissues in wild-type (WT) mice by 7 d after the infection but was not expressed in uninfected mice. Dentoalveolar infections of IL-17RA knockout (KO) mice demonstrated significantly increased bone destruction and more abscess formation in the apical area compared with WT mice. Infected IL-17RA KO mice exhibited significantly increased neutrophils and macrophages compared with the WT littermates at day 21, suggesting a failure of transition from acute to chronic inflammation in the IL-17RA KO mice. The expression of IL-1 (both α and β isoforms) and MIP2 were significantly upregulated in the IL-17RA KO compared with WT mice at day 21 postinfection. The development of periapical lesions in IL-17RA KO mice was significantly attenuated by neutralization of IL-1β and MIP2. Taken together, these results demonstrate that IL-17RA signal seems to be protective against infection-induced periapical inflammation and bone destruction via suppression of neutrophil and mononuclear inflammation.
authors.affiliation: Department of Restorative Dental Sciences, College of Dentistry, University of Dammam, 1982 Dammam, Saudi Arabia.
authors.forename: Emad
authors.initials: E
authors.lastname: AlShwaimi
authors.forename: Ellen
authors.initials: E
authors.lastname: Berggreen
authors.forename: Hisako
authors.initials: H
authors.lastname: Furusho
authors.forename: Jonathan Caleb
authors.initials: JC
authors.lastname: Rossall
authors.forename: Justine
authors.initials: J
authors.lastname: Dobeck
authors.forename: Subbiah
authors.initials: S
authors.lastname: Yoganathan
authors.forename: Philip
authors.initials: P
authors.lastname: Stashenko
authors.forename: Hajime
authors.initials: H
authors.lastname: Sasaki
mesh_terms: D016301:Alveolar Bone Loss / Q000209:etiology / Q000276:immunology / Q000517:prevention & control*; D000818:Animals; D001862:Bone Resorption / Q000209:etiology / Q000276:immunology / Q000517:prevention & control*; D054426:Chemokine CXCL2 / Q000096:biosynthesis / Q000235:genetics; D002908:Chronic Disease; D060085:Coinfection; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D005786:Gene Expression Regulation / Q000276:immunology; D020381:Interleukin-17 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D053582:Interleukin-1alpha / Q000096:biosynthesis / Q000235:genetics; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000235:genetics; D017737:Macrophages, Peritoneal / Q000276:immunology*; D008297:Male; D008334:Mandible; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008963:Molar; D009504:Neutrophils / Q000276:immunology*; D010485:Periapical Periodontitis / Q000473:pathology*; D053722:Receptors, Interleukin-17 / Q000172:deficiency / Q000502:physiology*
chemical_list: D054426:Chemokine CXCL2; C404915:Cxcl2 protein, mouse; D016207:Cytokines; C491673:Il17ra protein, mouse; D020381:Interleukin-17; D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D053722:Receptors, Interleukin-17