1095 Gastroenterologist Care is Associated With Lower Mortality Risk in Hospitalized Ulcerative Colitis Patients

Abstract

of IP-10 and other pro-inflammatory chemokines (e.g. Fractalkine) via direct proteolytic cleavage. Interestingly, tissue culture experiments revealed that conditioned media of Lp (CM Lp) selectively degrades tissue-distributed IP-10, suggesting tissue-accessibility of CM Lp. Moreover, intraperitoneal injection experiments in an experimental ileitis model revealed that CM Lp reduces intestinal IP-10 levels, lymphocyte recruitment and ileal inflammation. LC-MS/MS analysis of fractionated CM Lp indicated prtP-encoded lactocepin as active probiotic protease of Lp. This could be confirmed by immunoprecipitated active prtPencoded lactocepin, which degraded IP-10. Generation of a prtP-disruption mutant (lactocepin-negative) from a similarly active, but transformable, human Lactobacillus casei (Lc) isolate resulted in loss of its IP-10 degrading capacity, confirming probiotic prtP-encoded lactocepin as the active structure. Finally, feeding studies in T cell transferred Rag2-/mice revealed, that the prtP-encoded lactocepin expressing Lc significantly reduces cecal IP-10 levels and cecal inflammation compared to the lactocepin-negative prtP-disruption mutant. Conclusion: We identified a probiotic prtP-encoded lactocepin as anti-inflammatory structure from a clinically relevant probiotic strain. This probiotic prtP-encoded lactocepin mediates antiinflammatory effects in tissue culture and mouse models of IBD via selective chemokine degradation.