Mechanisms of the innate defense regulator peptide 1002 anti-inflammatory activity in a sterile inflammation mouse model. Mus musculus

Innate defense regulator (IDR) peptide-1002 is a synthetic host defense peptide derivative with strong anti-inflammatory properties.To investigate the anti-inflammatory mechanisms of IDR-1002 in vivo, the phorbol 12-myristate 13-acetate (PMA)-induced mouse ear inflammation model was used. Topical IDR-1002 treatment successfully dampened PMA-induced ear edema, proinflammatory cytokine production, reactive oxygen and nitrogen species release, and neutrophil recruitment in the ears of CD1 mice. Advanced RNA-Seq analysis on the mouse ear transcriptome revealed that IDR-1002 reduced sterile inflammation by suppressing the expression of transmembrane G-protein coupled receptors (Class A/1 rhodopsin-like), including receptors for chemokines, prostaglandins, histamine, platelet activating factor and anaphylatoxin. IDR-1002 also dampened IFNγ response and repressed the Interferon regulatory factor (Irf) 8-regulated network that controls central inflammatory pathways. Overall design: RNA-Seq profiling of gene expression in mouse ear tissue exposed to three treatment conditions