The Role of Indole-3-Acetic Acid in Ameliorating Collagen-Induced Arthritis in Mice

Abstract

Background: This study aimed to investigate the role and possible mechanisms by which indole-3-acetic acid (IAA) mitigates inflammation in rheumatoid arthritis (RA). Method: Bovine type II collagen was injected to construct mice with collagen-induced arthritis (CIA) to simulate RA. IAA was adopted for the treatment of CIA mice by oral administration. The involvement of aryl hydrocarbon receptor (AhR) in the therapeutic efficacy of IAA was investigated through CH223191 (an AhR antagonist). The severity of paw inflammation was assessed using qualitative clinical scoring. In addition, we measured Cytochrome P450 1A1 (CYP1A1) expression and AhR mRNA and protein levels, along with the serum levels of cytokines. The percentage of Regulatory T (Treg) and T helper 17 (Th17) cells in spleens was examined by flow cytometry. Result: IAA treatment reduced paw swelling, erythema, and inflammation in CIA mice. CH223191 reduced the therapeutic effect of IAA, and reversed the decrease of serum levels of tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin (IL)-1β, IL-17A and IL-6 in IAA-induced CIA mice. The immunological imbalance was improved after IAA treatment in CIA mice. CH223191 reversed the decrease of Th17 cells in the spleen induced by IAA. Conclusion: IAA treatment reduced paw swelling, erythema, and inflammation of CIA mice and restored the immunological balance in the spleen by regulating AhR.