title: Expression of interleukin-33 and its receptor ST2 in periapical granulomas and radicular cysts.
abstract: BACKGROUND
  Interleukin-33 (IL-33) is a recently identified cytokine belonging to the IL-1 family and ligand for the IL-1 receptor-related protein ST2. IL-33/ST2 signaling plays a critical role in allergy, autoimmunity, and chronic inflammatory disorders, but its role in the pathogenesis of periapical lesions is unknown. We aimed to investigate the expression patterns of IL-33 and ST2 in human periapical lesions.
  
  
  METHODS
  Periapical lesions (n = 36) and healthy periapical tissues (n = 10) were evaluated by immunohistochemistry using antibodies specific for human IL-33 and ST2. Lesion samples were further analyzed by double immunofluorescence to assess IL-33/ST2 co-expression.
  
  
  RESULTS
  The numbers of IL-33- and ST2-positive fibroblasts were significantly higher in periapical lesions compared to healthy periapical tissues (both P < 0.05), while the numbers of IL-33- and ST2-positive endothelial cells were similar (both P > 0.05). There were no significant differences in the numbers of IL-33- and ST2-positive fibroblasts and endothelial cells between periapical granulomas and radicular cysts (all P > 0.05). Similarly, numbers of ST2-positive mononuclear cells did not differ between periapical granulomas and radicular cysts (P > 0.05). The majority of epithelial cells in radicular cysts were IL-33 positive, while the small proportion of epithelial cells was ST2 positive. Double immunofluorescence analysis revealed IL-33/ST2 co-expression in fibroblasts and endothelial cells.
  
  
  CONCLUSIONS
  IL-33 and ST2 are expressed in periapical granulomas and radicular cysts. Increased numbers of IL-33- and ST2-positive fibroblasts in periapical lesions when compared to healthy periapical tissues suggest that IL-33/ST2 signaling may be involved in periapical inflammation and tissue fibrosis.
authors: Center for Molecular Medicine, Kragujevac, Serbia.
authors: Milena
authors: M
authors: Velickovic
authors: Center for Molecular Medicine, Kragujevac, Serbia.
authors: Nada
authors: N
authors: Pejnovic
authors: Department of Endodontics, Faculty of Stomatology, University of Belgrade, Belgrade, Serbia.
authors: Renata
authors: R
authors: Petrovic
authors: Center for Molecular Medicine, Kragujevac, Serbia.
authors: Slobodanka
authors: S
authors: Mitrovic
authors: Center for Molecular Medicine, Kragujevac, Serbia.
authors: Ilija
authors: I
authors: Jeftic
authors: Department of Preventive and Pediatric Dentistry, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia.
authors: Tatjana
authors: T
authors: Kanjevac
authors: Department of Endodontics, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia.
authors: Aleksandra
authors: A
authors: Lukic
mesh_terms: D000293:Adolescent; D000328:Adult; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism; D004847:Epithelial Cells / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation; D000072179:Interleukin-1 Receptor-Like 1 Protein / Q000096:biosynthesis* / Q000378:metabolism; D000067596:Interleukin-33 / Q000096:biosynthesis* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010484:Periapical Granuloma / Q000378:metabolism* / Q000473:pathology; D011842:Radicular Cyst / Q000378:metabolism* / Q000473:pathology; D055815:Young Adult
chemical_list: D016207:Cytokines; C079241:IL1RL1 protein, human; C506536:IL33 protein, human; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33
keywords: ST2; inflammation; interleukin-33; periapical granuloma; radicular cyst