KA-1002, a Novel Lysophosphatidic Acid Signaling Antagonist, Alleviates Bovine Tracheal Cell Disruption and Inflammation

SIMPLE SUMMARY: Bovine respiratory diseases are a key factor reducing the productivity of cows in an industrial livestock environment. We have identified a novel lysophosphatidic acid signaling antagonist, KA-1002, which alleviates lysophosphatidic acid-mediated bovine tracheal cell disruptive tissue injury and inflammation. KA-1002 could be considered a novel therapeutic reagent candidate for maintaining respiratory health in reared cattle. ABSTRACT: The industrial livestock environment can cause stress and weakened immunity in cattle, leading to microbial infections which reduce productivity. As such, there is a need for an effective therapeutic agent that can alleviate uncontrolled destructive respiratory inflammation. We found that lysophosphatidic acid (LPA), a potent endogenous stress-induced inflammatory agent, causes respiratory tissue damage and triggers inflammation in bovine bronchial cells. LPA also inflames pulmonary bovine blood vessel cells to produce inflammatory cytokines. These findings strongly suggest that LPA is a highly important endogenous material exacerbating bovine respiratory diseases. We further identified a novel LPA-signaling antagonist, KA-1002, and showed that it alleviated LPA-mediated bovine tracheal cell disruption and inflammation. Therefore, KA-1002 could potentially serve as a novel therapeutic agent to maintain physiologically healthy and balanced conditions in bovine respiratory tracts.