Anti-inflammatory effects of ursodeoxycholic acid by lipopolysaccharide-stimulated inflammatory responses in RAW 264.7 macrophages

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.

Liver Macrophages: Old Dogmas and New Insights

“…(120) UDCA was also shown to reduce TNFα-induced IL-8 production by macrophages associated with a reduction in TNFα receptorassociated factor 2 (TRAF2) phosphorylation (121) and to reduce LPS-induced macrophage activation. (122)(123)(124) Although all cells in one organism possess the same genetic material, gene expression modulation through epigenetic modifications controlled by histone remodeling, transcription factors, miRNAs, and long noncoding RNAs results in a plethora of distinct cell types. Recent studies have highlighted that macrophages are not exempt from these epigenetic modifications because they directly affect the polarization state of macrophages.…”

Propofol inhibits the release of interleukin-6, 8 and tumor necrosis factor-α correlating with high-mobility group box 1 expression in lipopolysaccharides-stimulated RAW 264.7 cells

“…Previous studies have used the model of ischemia-reperfusion injury to explore the inflammatory process and found that propofol exhibited antioxidant and anti-inflammatory effects [ 1 – 5 ]. Lipopolysaccharide (LPS) is the major cause of clinical fever, it is also the key factor that cause the shock, sepsis, cholera, and other diseases like adult respiratory syndrome, multiple organ failure, or the pathological processes [ 6 ]. Gram-negative bacteria are often used to induce inflammation in vitro, and studies have shown that LPS is a major component of the outer membrane of Gram-negative bacteria [ 6 ].…”

“…Lipopolysaccharide (LPS) is the major cause of clinical fever, it is also the key factor that cause the shock, sepsis, cholera, and other diseases like adult respiratory syndrome, multiple organ failure, or the pathological processes [ 6 ]. Gram-negative bacteria are often used to induce inflammation in vitro, and studies have shown that LPS is a major component of the outer membrane of Gram-negative bacteria [ 6 ]. Studies have confirmed that high-mobility group box 1 (HMGB1) is a DNA-binding protein that maintains nucleosomal structures and regulates gene transcription, which is characterized by highly conserved proteins.…”

Postoperative pain pathophysiology and treatment strategies after CRS + HIPEC for peritoneal cancer

“…When surgical injury causes nerve damages, the microglia in the spinal cord and brainstem are activated by surface P2 receptors, chemokine receptors, and toll-like receptors (TLRs). The activated small microglia can release a series of inflammatory factors (IL-1β, IL-6, and TNF-α) that mediate neuroinflammatory responses, leading to central sensitization [27].…”