Characterization of chenodeoxycholic acid as an endogenous antagonist of the G-coupled formyl peptide receptors

Inflamm Res. 2000 Dec;49(12):744-55. doi: 10.1007/s000110050656.


Objective and design: To demonstrate the role of bile acids in immune modulation we examined the ability of select bile acids to inhibit leukocyte migration and chemoattractant receptor function.

Materials: To elucidate this mechanism, we employed primary human monocytes, neutrophils and cell lines transfected to express either the high affinity fMLP receptor (FPR) or the low affinity fMLP receptor like 1 (FPRL1).

Treatment: Cells were treated with chenodeoxycholic acid (CDCA) and related bile acids in a 0-400 micromolar range.

Method: Cell viability, chemotaxis and calcium flux analysis were preformed.

Results: We observed that pathophysiological levels (< or = 150 micromolar) of CDCA competitively inhibited 3H-fMLP binding to human monocytes, FPR and FPRL1 transfected cells. Additionally, CDCA reduced both the chemotactic and calcium flux responses induced by fMLP or "W" peptide. Further, CDCA inhibited anti-FPR antibody binding to monocytes.

Conclusions: CDCA selectively inhibited human leukocyte chemotaxis and calcium flux induced by fMLP, but not other chemoattractants, suggesting a mechanism for inhibition of inflammation and suppression of innate immune response.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Calcium / metabolism
  • Cell Survival
  • Cells, Cultured
  • Chemotaxis, Leukocyte / physiology
  • Chenodeoxycholic Acid / antagonists & inhibitors
  • Chenodeoxycholic Acid / pharmacology*
  • Flow Cytometry
  • GTP-Binding Proteins / antagonists & inhibitors*
  • Humans
  • Indicators and Reagents
  • Receptors, Formyl Peptide
  • Receptors, Immunologic / antagonists & inhibitors*
  • Receptors, Lipoxin*
  • Receptors, Peptide / antagonists & inhibitors*


  • FPR2 protein, human
  • Indicators and Reagents
  • Receptors, Formyl Peptide
  • Receptors, Immunologic
  • Receptors, Lipoxin
  • Receptors, Peptide
  • Chenodeoxycholic Acid
  • GTP-Binding Proteins
  • Calcium