The Role of Bile Acid Receptors in Chronic Inflammatory Diseases

With recent developments, biologic therapies has shown superior efficacy for rheumatic diseases compared with preexisting pharmacologic therapies, which are associated with high costs, non-response in certain patient groups, and severe adverse effects such as infections limiting their wide-spread use and revealing a need for the development of novel treatments. Since discovering the role of bile acid receptors in regulating inflammation, clinical trials evaluating the use of bile acid receptor agonists as a means to potentially treat various inflammatory disorders, such as alcoholic hepatitis, non-alcoholic steatohepatitis, primary biliary cirrhosis, primary sclerosing cholangitis have been ongoing. This review summarizes the results of studies on the anti-inflammatory effects and mechanisms of bile acid receptors and the results of previous to date looking at the use of bile acid receptor agonists in animal models of inflammatory disorders and clinical trials. Furthermore, we present the potentials of the bile acid receptor agonists in the treatment of inflammatory rheumatic diseases, including rheumatoid arthritis.

Gene Expression Profile in Patients with Axial Spondyloarthritis: Meta-analysis of Publicly Accessible Microarray Datasets

OBJECTIVE: To identify a gene expression signature in axial spondyloarthritis/ankylosing spondylitis (SpA/AS) and genomic pathways likely to be involved in pathogenesis of SpA/AS patients. METHODS: Four publicly accessible microarray studies from SpA/AS patients were integrated, and a transcriptomic and network-based meta-analysis was performed. This meta-analysis was compared with a published microarray study in whole blood of AS patients. RESULTS: According to our meta-analysis, 1,798 genes were differentially expressed in the whole blood of SpA/AS patients compared to healthy controls, while 674 genes were differentially expressed in the synovium of SpA/AS patients compared to healthy controls. When the whole blood meta-analysis data was compared with a published microarray study that also analyzed whole blood in SpA/AS patients, pathways involved in Toll-like receptor signaling, osteoclast differentiation, T cell receptor signaling and janus kinase–signal transducer and activator of transcription (Jak-STAT) signaling were often enriched in SpA/AS. On the other hand, eomesodermin, RUNX3, and interleukin-7 receptor (IL7R) were usually decreased in SpA/AS patients, suggesting that deficiency of these genes contributes to increased IL-17 production in AS. CONCLUSION: Several common enrichment pathways including Toll-like receptor signaling pathway, osteoclast differentiation, T cell receptor signaling pathway and Jak-STAT signaling pathway were identified in the differentially expressed genes of whole blood and synovium from SpA/AS patients, suggesting that these pathways are involved in the pathogenesis of SpA/AS.