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PLoS One. 2016 Dec 19;11(12):e0168080. doi: 10.1371/journal.pone.0168080. eCollection 2016.

Interleukin-33 and RANK-L Interplay in the Alveolar Bone Loss Associated to Periodontitis.

Lapérine O1,2,3, Cloitre A1,2,3,4, Caillon J5, Huck O6,7, Bugueno IM6, Pilet P1,2,3,4, Sourice S1,2,3, Le Tilly E1,2,3, Palmer G8,9, Davideau JL6,7, Geoffroy V10,11, Guicheux J1,2,3,4, Beck-Cormier S1,2,3, Lesclous P1,2,3,4.

Author information

1
INSERM, U791, LIOAD, Nantes, France.
2
Université de Nantes, UMR-S 791, LIOAD, Nantes, France.
3
UFR Odontologie, Nantes, France.
4
ONIRIS, UMR-S 791, LIOAD, Nantes, France.
5
EA 3826 Thérapeutiques cliniques et expérimentales des infections, Nantes, France.
6
INSERM, U1109 Osteoarticular & Dental Regenerative Nanomedicine, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, France.
7
Département de Parodontologie, Faculté de Chirurgie Dentaire, Université de Strasbourg, Strasbourg, France.
8
Division of Rheumatology, Department of Internal Medicine Specialties, University Hospitals of Geneva, Geneva, Switzerland.
9
Department of Pathology-Immunology, University of Geneva, School of Medicine, Geneva, Switzerland.
10
INSERM U1132 BIOSCAR, Hôpital Lariboisière, Paris, France.
11
Université Paris Diderot, Sorbonne Paris Cité, Paris, France.

Abstract

INTRODUCTION:

Chronic Periodontitis (CP) is an inflammatory disease of bacterial origin that results in alveolar bone destruction. Porphyromonas gingivalis (Pg), one of the main periopathogens, initiates an inflammatory cascade by host immune cells thereby increasing recruitment and activity of osteoclasts, the bone resorbing cells, through enhanced production of the crucial osteoclastogenic factor, RANK-L. Antibodies directed against some cytokines (IL-1β, IL-6 and TNF-α) failed to exhibit convincing therapeutic effect in CP. It has been suggested that IL-33, could be of interest in CP.

OBJECTIVE:

the present study aims to analyze whether and how IL-33 and RANK-L and/or their interplay are involved in the bone destruction associated to CP.

MATERIAL AND METHODS:

mRNAs and protein expressions of IL-33 and RANK-L were analyzed in healthy and CP human gingival samples by immunohistochemistry (IHC) and RT-qPCR. Murine experimental periodontitis (EP) was induced using Pg infected ligature and Pg free ligature around the first maxillary molar. Alveolar bone loss was recorded by μCT. Mouse gingival explants were stimulated for 24 hours with IL-33 and RANK-L mRNA expression investigated by RT-qPCR. Human oral epithelial cells were infected by Pg for 6, 12; 24 hours and IL-33 and RANK-L mRNA expressions were analyzed by RT-qPCR.

RESULTS:

IL-33 is overexpressed in gingival epithelial cells in human affected by CP as in the murine EP. In human as in murine gingival cells, RANK-L was independently induced by Pg and IL-33. We also showed that the Pg-dependent RANK-L expression in gingival epithelial cells occured earlier than that of IL-33.

CONCLUSION:

Our results evidence that IL-33 overexpression in gingival epithelial cells is associated with CP and may trigger RANK-L expression in addition to a direct effect of Pg. Finally, IL-33 may act as an extracellular alarmin (danger signal) showing proinflammatory properties in CP perpetuating bone resorption induced by Pg infection.

PMID:
27992569
PMCID:
PMC5167367
DOI:
10.1371/journal.pone.0168080
[Indexed for MEDLINE]
Free PMC Article

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