title: Peroxisome proliferator-activated receptor-γ and thymic stromal lymphopoietin are involved in the pathophysiology of childhood coeliac disease.
abstract: Celiac disease (CD) is a chronic autoimmune enteropathy caused by exposure to dietary gluten in genetically predisposed individuals. The transcription factor peroxisome proliferator-activated receptor gamma (PPARγ) was shown to exert protective effects in several immune-mediated disorders. Activation of PPARγ suppressed the expression of thymic stromal lymphopoietin (TSLP), an inducer of proinflammatory cytokines. Since the role of TSLP in gluten-sensitive enteropathy is completely unknown, we investigated the involvement of TSLP and its regulator PPARγ in childhood CD. We collected duodenal biopsy specimens from 19 children with newly diagnosed CD, 6 children with treated CD (gluten-free diet, GFD), and 10 controls. Expression of mRNA and protein levels of PPARγ, TSLP, and TSLP receptor were determined by real-time RT-PCR and Western blot, respectively. Duodenal localization of PPARγ and TSLP was studied by immunohistochemistry. In duodenal mucosa of children with CD, the amount of PPARγ was significantly lower and simultaneously that of TSLP significantly higher compared to controls (p < 0.05). In GFD-treated patients, the levels of PPARγ mRNA and protein were significantly higher while that of TSLP markedly lower compared to newly diagnosed CD (p < 0.05). Immunohistochemistry revealed PPARγ and TSLP expression in lamina propria immune cells and in enterocytes. Low expression of PPARγ and high expression of TSLP in the duodenal mucosa of children with newly diagnosed CD suggest that they are involved in the pathophysiology of CD. We hypothesize that PPARγ may be an inhibitory regulator of TSLP-stimulated inflammatory processes in CD.
authors.affiliation: MTA-SE, Pediatrics and Nephrology Research Group, Budapest, Hungary.
authors.forename: Erna
authors.initials: E
authors.lastname: Sziksz
authors.forename: Kriszta
authors.initials: K
authors.lastname: Molnár
authors.forename: Rita
authors.initials: R
authors.lastname: Lippai
authors.forename: Domonkos
authors.initials: D
authors.lastname: Pap
authors.forename: Anna
authors.initials: A
authors.lastname: Onody
authors.forename: Apor
authors.initials: A
authors.lastname: Veres-Székely
authors.forename: Péter
authors.initials: P
authors.lastname: Vörös
authors.forename: Dolóresz
authors.initials: D
authors.lastname: Szabó
authors.forename: Hajnalka
authors.initials: H
authors.lastname: Győrffy
authors.forename: Gábor
authors.initials: G
authors.lastname: Veres
authors.forename: Tivadar
authors.initials: T
authors.lastname: Tulassay
authors.forename: Adám
authors.initials: A
authors.lastname: Vannay
authors.forename: András
authors.initials: A
authors.lastname: Arató
mesh_terms: D000293:Adolescent; D015153:Blotting, Western; D002446:Celiac Disease / Q000178:diet therapy / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000378:metabolism*; D055050:Diet, Gluten-Free; D004386:Duodenum / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000473:pathology; D008297:Male; D047495:PPAR gamma / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D016207:Cytokines; D047495:PPAR gamma; D000094632:Thymic Stromal Lymphopoietin