INVESTIGADORES
CHIRDO Fernando Gabriel
congresos y reuniones científicas
Título:
Expression of CXCR3 in human intestinal mucosa
Autor/es:
RULLI E; ALLEGRETTI Y; BONDAR C; GUZMAN L; CUETO RUA E; DRUT E; CHIRDO F
Lugar:
Amsterdam
Reunión:
Congreso; 13th International Coeliac Disease Symposium; 2009
Institución organizadora:
International Coeliac Disease Symposium
Resumen:
Interaction between
gliadin and the intestinal epithelium results in increased permeability to
macromolecules present in the gut lumen, leading to the activation of innate
and, later, adaptive immunity. In coeliac disease (CD), early pathogenic events
involve changes such as disruption of tight junction integrity and production
of proinflammatory cytokines, such as IL-15, which plays a major role on this
stage.
CXCR3 is a chemokine
receptor, which interacts with CXCL10 (IP-10) among other ligands. Recently, it
was reported that CXCR3 acts as a mucosal gliadin receptor and is responsible
for gliadin-induced disruption of intestinal permeability.
The aim of this study
was to evaluate the expression of CXCR3 and to test different inducers of its
expression in whole biopsies from paediatric CD patients and controls (as
assessed by histology and serology).
The expression of
CXCR3, IFN-g and
CXCL10 was analysed by Real-Time qPCR. CXCR3 inducibility was also investigated
on THP-1 cells stimulated with the a-gliadin p31-43 peptide (known to trigger
innate immunity mechanisms), IL-15, flagellin (TLR5 ligand), poly I:C (TLR3
ligand) and a combination of p31-43 and IL-15.
As expected, the
mucosal samples from CD patients showed a significant increase in IFN-g mRNA levels when
compared to non-CD controls. The expression of CXCR3 and CXCL10 was found
slightly, but not significantly, elevated in CD patients. Treatment of THP-1
cells with p31-43, IL-15, poly I:C or flagellin had no effect on the expression
of CXCR3. Interestingly, a 4-fold increase in CXCR3 mRNA levels was observed
when a combination of p31-43 and IL-15 was used to stimulate the cells.