Abstract
Simple SummaryInflammatory 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.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.
Highlights
Various inflammatory diseases including livestock animal respiratory diseases are very common and potent destructive issues on the animal industry [1,2,3], and are caused by various environmental stresses from microbial infections, crowding, and dust [1,2,3,4]
To investigate a genome-scale transcriptional expression pattern on swine macrophages differentially regulated by lysophosphatidic acid (LPA) and KA-1002 treatment, we analyzed gene expression profiles on a genome-wide scale of LPA-treated (LPA) and LPA plus KA-1002 treated swine macrophage cell line, 3D4/21 compared to untreated 3D4/21 cells
We found that significant changes on genome scaled transcription in LPA treated swine macrophages compared to untreated swine macrophages
Summary
Various inflammatory diseases including livestock animal respiratory diseases are very common and potent destructive issues on the animal industry [1,2,3], and are caused by various environmental stresses from microbial infections, crowding, and dust [1,2,3,4]. Inflammatory respiratory diseases are highly common in modern pork production worldwide and are often referred to as porcine respiratory disease complex (PRDC) [5,6]. For those various inflammatory diseases, endogenous factors associated with those environmental stresses are important and those inflammatory endogenous factors often weaken immunity of animals leading to susceptibility to pathogenic invasion. Among various endogenous stress-induced molecules, lysophosphatidic acid (LPA) is a powerful endogenous trigger of inflammation in a number of diseases-associated conditions [7,8,9,10].
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