IL-1B; blockade prevents cell death and mucosal damage of the small intestine in a model of sterile inflammation.

RUERA CAROLINA; MICULÁN, EMANUEL; DUCCA, GERÓNIMO; PEREZ, FEDERICO; IRIBARREN MARÍA LUZ; CARASI, PAULA; CHIRDO FERNANDO

IMMUNOLOGY LETTERS

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2022

0165-2478

The intestinal mucosa is covered by a layer of epithelial cells that is constantly challenged bycommensal, opportunistic, and pathogenic microorganisms, their components, and harmfulcompounds. Any inflammatory response to these materials must be tightly controlled to limit tissuedamage and restore the integrity of the mucosal barrier. We have shown previously that production ofIL-1β via activation of the inflammasome can lead to mucosal damage in the small intestinal pathologythat occurs after intragastric administration of a gluten derived peptide, p31-43. Here we show thatspecific inhibition of caspase-1 or NLRP3 abolishes the damage induced by p31-43, and thatantibody-mediated blocking of IL-1β inhibits the both the histological changes and the induction ofapoptosis and caspase-3 activation driven by p31-43. Understanding the role of IL-1β in sterileinflammation may help to understand chronic inflammatory pathological processes, and design newintervention strategies.