Abstract

PurposeThe aim of this study was to investigate the anti-inflammatory effects of Ursodeoxycholic acid (UDCA) in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages.MethodsWe induced an inflammatory process in RAW 264.7 macrophages using LPS. The anti-inflammatory effects of UDCA on LPS-stimulated RAW 264.7 macrophages were analyzed using nitric oxide (NO). Pro-inflammatory and anti-inflammatory cytokines were analyzed by quantitative real time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA). The phosphorylations of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 in mitogen-activated protein kinase (MAPK) signaling pathways and nuclear factor kappa-light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα) signaling pathways were evaluated by western blot assays.ResultsUDCA decreased the LPS-stimulated release of the inflammatory mediator NO. UDCA also decreased the pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin 1-α (IL-1α), interleukin 1-β (IL-1β), and interleukin 6 (IL-6) in mRNA and protein levels. In addition, UDCA increased an anti-inflammatory cytokine interleukin 10 (IL-10) in the LPS-stimulated RAW 264.7 macrophages. UDCA inhibited the expression of inflammatory transcription factor nuclear factor kappa B (NF-κB) in LPS-stimulated RAW 264.7 macrophages. Furthermore, UDCA suppressed the phosphorylation of ERK, JNK, and p38 signals related to inflammatory pathways. In addition, the phosphorylation of IκBα, the inhibitor of NF-κB, also inhibited by UDCA.ConclusionUDCA inhibits the pro-inflammatory responses by LPS in RAW 264.7 macrophages. UDCA also suppresses the phosphorylation by LPS on ERK, JNK, and p38 in MAPKs and NF-κB pathway. These results suggest that UDCA can serve as a useful anti-inflammatory drug.

Highlights

  • Inflammatory response is a physiological process against detrimental stimuli such as pathogens in our bodies [1] and macrophages play a critical role in inflammatory responses through the production of various cytokines [2]

  • Ursodeoxycholic acid (UDCA) suppressed the phosphorylation of extracellular signal-regulated kinase (ERK), Jun N-terminal kinase (JNK), and p38 signals related to inflammatory pathways

  • UDCA suppresses the phosphorylation by LPS on ERK, JNK, and p38 in mitogen-activated protein kinase (MAPK) and NF-κB pathway

Read more

Summary

Introduction

Inflammatory response is a physiological process against detrimental stimuli such as pathogens in our bodies [1] and macrophages play a critical role in inflammatory responses through the production of various cytokines [2]. Excessive inflammatory response can lead to many diseases such as atherosclerosis [7], rheumatoid arthritis [8], and asthma [9]. Ursodeoxycholic acid (UDCA), used as a Chinese medicine for more than 3000 years [13], has been studied for its alleviating effects on atherosclerosis, diabetes, and renal disease [14]. To the best of our knowledge, only one study conducted an evaluation of UDCA as an anti-inflammatory drug in a lipopolysaccharide (LPS)-stimulated inflammatory process model [18]. Joo et al investigated the anti-inflammatory effects of UDCA through the NO test and with IL-1β. Based on their findings, they suggested that UDCA could inhibit the inflammatory process of microglial cells [18]. Studies with only NO and IL-1β expression levels may not sufficiently support the authors’ claims

Objectives
Methods
Results
Conclusion
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call