Taurolithocholic acid but not tauroursodeoxycholic acid rescues phagocytosis activity of bone marrow‐derived macrophages under inflammatory stress

Journal of Cellular Physiology, 2022 · DOI: 10.1002/jcp.30619 · Published: March 1, 2022

Simple Explanation

Spinal cord injuries (SCI) lead to cell death and myelin breakdown, which inhibits axon regeneration. Macrophages help remove myelin debris, but inflammation can impair this process. This study investigates how the inflammatory state of macrophages impacts their myelin phagocytosis ability. The research explores whether specific bile acids can improve myelin clearance in macrophages under inflammatory stress. They tested taurolithocholic acid (TLCA), tauroursodeoxycholic acid (TUDCA) and hyodeoxycholic acid (HDCA) to see if they could counteract the effects of inflammation on myelin uptake. The study found that only TLCA rescued myelin phagocytosis in bone marrow-derived macrophages (BMDM) when it was suppressed by inflammatory stimuli. This effect was linked to TGR5-PKA signaling, suggesting that activating bile acid receptors could enhance myelin clearance in neuropathologies.

Study Duration

Not specified

Participants

Adult male C57BL/6 mice, adult Wistar rats

Evidence Level

In vitro study

Key Findings

1
Activation of the TLR4-NFκB pathway reduced myelin uptake by bone marrow-derived macrophages (BMDM), while IFNγ-Jak/STAT1 signaling did not.
2
In BMDM, only taurolithocholic acid (TLCA) rescued myelin phagocytosis when suppressed by lipopolysaccharides (LPS).
3
Inhibition of protein kinase A (PKA) blocked the effect of TLCA, implicating TGR5-PKA signaling in the effect of TLCA.

Research Summary

The study investigates the effect of inflammatory stimuli and bile acids on myelin clearance by macrophages. Activation of the LPS-TLR4/NFκB pathway reduces myelin phagocytosis by bone marrow-derived macrophages (BMDM) in vitro, while IFNγ-Jak/STAT1 signaling does not. Taurolithocholic acid rescues myelin phagocytosis in BMDM when this activity is suppressed by LPS. The FXR agonist GW4604 did not increase phagocytosis in the presence or absence of LPS, while, on the other hand, an inhibitor of PKA blocked the effect of TLCA. Activation of bile acid receptors may therefore be explored for therapeutic strategies to improve myelin clearance in pathologies such as SCI, where this is a limiting factor.

Practical Implications

Therapeutic Potential

Activation of bile acid receptors, particularly TGR5, may be a therapeutic target for improving myelin clearance in spinal cord injury and other neuropathologies.

Targeted Therapies

Developing therapies that specifically enhance TGR5-PKA signaling in macrophages could improve myelin clearance and reduce inflammation.

Further Research

Future research should focus on identifying TLCA analogues or other compounds that can effectively activate TGR5 signaling without causing adverse effects such as liver cholestasis.

Taurolithocholic acid but not tauroursodeoxycholic acid rescues phagocytosis activity of bone marrow‐derived macrophages under inflammatory stress

Simple Explanation

Key Findings

Research Summary

Practical Implications

Therapeutic Potential

Targeted Therapies

Further Research

Study Limitations

Your Feedback

Was this summary helpful?

Taurolithocholic acid but not tauroursodeoxycholic acid rescues phagocytosis activity of bone marrow‐derived macrophages under inflammatory stress

Simple Explanation

Key Findings

Research Summary

Practical Implications

Therapeutic Potential

Targeted Therapies

Further Research

Study Limitations

Your Feedback

Was this summary helpful?