A Novel Therapeutic Reagent, KA-1002 for Alleviating Lysophosphatidic Acid-Mediated Inflammation Related Gene Expression in Swine Macrophages

SIMPLE SUMMARY: Inflammatory diseases are a key factor reducing the productivity of animals in a livestock industrial environment. We have identified a novel lysophosphatidic acid signaling antagonist, KA-1002, which alleviates lysophosphatidic acid-mediated a broad range of inflammation related gene expression in swine macrophages. Specifically, we found that KA-1002 significantly alleviated LPA-induced genes related with inflammation such as a role of macrophages, fibroblasts and endothelial cells in rheumatoid arthritis and STAT3 signal pathway. Taken together, KA-1002 could be considered a novel therapeutic reagent candidate for swine inflammatory diseases. ABSTRACT: Stresses and various infectious reagents caused multiple inflammatory diseases in swine in a livestock industrial environment. Therefore, there is a need for an effective therapeutic or preventive agent that could alleviate chronic and acute inflammation. We found that lysophosphatidic acid (LPA), a stress-induced potent endogenous inflammatory molecule, causes a broad range-regulation of inflammation related genes inflammation in swine macrophages. We further investigated the genome scaled transcriptional regulatory effect of a novel LPA-signaling antagonist, KA-1002 on swine macrophages, inducing the alleviated LPA-mediated inflammation related gene expression. Therefore, KA-1002 could potentially serve as a novel therapeutic or preventive agent to maintain physiologically healthy and balanced conditions of pigs.