TGR 5 signalling inhibits the production of pro‐inflammatory cytokines by in vitro differentiated inflammatory and intestinal macrophages in Crohn's disease

Abstract

Summary Bile acids ( BA s) play important roles not only in lipid metabolism, but also in signal transduction. TGR 5, a transmembrane receptor of BA s, is an immunomodulative factor, but its detailed mechanism remains unclear. Here, we aimed to delineate how BA s operate in immunological responses via the TGR 5 pathway in human mononuclear cell lineages. We examined TGR 5 expression in human peripheral blood monocytes, several types of in vitro differentiated macrophages (Mϕs) and dendritic cells. Mϕs differentiated with macrophage colony‐stimulating factor and interferon‐γ (Mγ‐Mϕs), which are similar to the human intestinal lamina propria CD 14 + Mϕs that contribute to Crohn's disease ( CD ) pathogenesis by production of pro‐inflammatory cytokines, highly expressed TGR 5 compared with any other type of differentiated Mϕ and dendritic cells. We also showed that a TGR 5 agonist and two types of BA s, deoxycholic acid and lithocholic acid, could inhibit tumour necrosis factor‐α production in Mγ‐Mϕs stimulated by commensal bacterial antigen or lipopolysaccharide. This inhibitory effect was mediated by the TGR 5– cAMP pathway to induce phosphorylation of c‐ F os that regulated nuclear factor‐κ B p65 activation. Next, we analysed TGR 5 levels in lamina propria mononuclear cells ( LPMC s) obtained from the intestinal mucosa of patients with CD . Compared with non‐inflammatory bowel disease, inflamed CD LPMC s contained more TGR 5 transcripts. Among LPMC s, isolated CD 14 + intestinal Mϕs from patients with CD expressed TGR 5. In isolated intestinal CD 14 + Mϕs, a TGR 5 agonist could inhibit tumour necrosis factor‐α production. These results indicate that TGR 5 signalling may have the potential to modulate immune responses in inflammatory bowel disease.

Shown for reading. Its publisher allows quoting it, not republishing it.

Cited by papers we hold 9

• Bile acid metabolism and signaling in health and disease: molecular mechanisms and therapeutic targets · 2024
  No notice
• The Emerging Role of Bile Acids in the Pathogenesis of Inflammatory Bowel Disease · 2022
  No notice
• Impact of Microbial Metabolites on Microbiota–Gut–Brain Axis in Inflammatory Bowel Disease · 2021
  No notice
• Bile Acid–Gut Microbiota Axis in Inflammatory Bowel Disease: From Bench to Bedside · 2021
  No notice
• Gut Microbiota in Hypertension and Atherosclerosis: A Review · 2020
  No notice
• Scutellariae Radix and Coptidis Rhizoma Improve Glucose and Lipid Metabolism in T2DM Rats via Regulation of the Metabolic Profiling and MAPK/PI3K/Akt Signaling Pathway · 2018
  No notice
• Bile Acids Activated Receptors Regulate Innate Immunity · 2018
  No notice
• Lithocholic acid controls adaptive immune responses by inhibition of Th1 activation through the Vitamin D receptor · 2017
  No notice
• TGR5, Not Only a Metabolic Regulator · 2016
  No notice

Reads

A person counts once a day per paper. We keep no cookie and no address: a reader is a hash that changes every day. Any month under five reads shows no number.