Inflammation is present, persistent and more sensitive to proinflammatory triggers in celiac disease enterocytes

PORPORA M; CONTE M; LANIA G; BELLOMO C; CHIRDO FG; AURICCHIO R; TRONCONE, RICCARDO; AURICCHIO S; BARONE MV; NANAYAKKARA M

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

MOLECULAR DIVERSITY PRESERVATION INTERNATIONAL-MDPI

Lugar: Basel; Año: 2022

1422-0067

Background & Aim Celiac disease (CD) is a chronic inflammatory disease caused by a genetic predisposition to an abnor-mal T cell mediated immune response to the gluten in the diet. Different environmental proinflamma-tory factors can influence and amplify the T cell mediated response to gluten. The aim of this manu-script was to study the role of enterocytes in CD intestinal inflammation and the response to different proinflammatory factors, such as gliadin and viruses. Material and Methods Intestinal biopsies from CD patients on gluten-containing (GCD-CD) or gluten-free diet (GFD-CD) as well as biopsies from potential CD patients (Pot-CD) before the onset of intestinal lesions and controls (CTR) were used to investigate IL-1β and IL-6 mRNA levels in situ. Organoids from CD patients were used to test the levels of NF-κB, ERK, IL-6, and IL-1β by Western blot (WB), ELISA and quantitative PCR. The Toll-like receptor ligand loxoribine (Lox) and gliadin peptide P31-43 were used as proinflammatory stimuli. Results In CD biopsies inflammation markers IL-1β and IL-6 were increased in the enterocytes, also in Pot-CD before the onset of the intestinal lesion and in GFD-CD. The inflammatory markers pNF-κB, pERK, IL-1β and IL-6 were increased and persistent in CD or-ganoids; these organoids were more sensitive to P31-43 and Lox stimuli compared with CTR organ-oids. Conclusions Taken together, these observations point to constitutive inflammation in CD enterocytes, which are more sensitive to inflammatory stimuli such as food components and viruses.