TRANSGENIC MOUSE MODEL HARBORING THE TRANSCRIPTIONAL FUSION CCL20-LUCIFERASE AS A NOVEL REPORTER OF PRO-INFLAMMATORY RESPONSE

MARTIN RUMBO; MARTINA CRISPO; JULIEN TABAREAU; DELPHINE CAYET; LAURYE VAN MAELE; ERREA AGUSTINA; FERREIRA ANA MARIA; JEAN CLAUDE SIRARD

Congreso; International Congress on Inflammation; 2013

Introduction: The chemokine CCL20, the unique ligand of CCR6 functions as an attractant of immune cells. Expression of CCL20 is induced by Toll-like Receptor (TLR) signaling or proinflammatory cytokine stimulation. However CCL20 is also constitutively produced at specific epithelial sites of mucosa. This expression profile is achieved by transcriptional regulation. The aim of the present work was to characterize regulatory features of mouse Ccl20 gene and to generate a transgenic reporter mice line using the Ccl20 promoter. Methods and Results: Transcriptional fusions between the mouse Ccl20 promoter and the firefly luciferase (luc) encoding gene were constructed and assessed in in vitro and in vivo assays. We found that liver CCL20 expression and luciferase activity were upregulated 110+/-15 and 123+/-22 fold respectively by systemic administration of the TLR5 agonist flagellin (n=8 for each group, three independent experiments with similar results). Using shRNA and dominant negative form specific for mouse TLR5, we showed that this expression was controlled by TLR5 (n=6, p