ReferenceID 6305
Taurolithocholic acid but not tauroursodeoxycholic acid rescues phagocytosis activity of bone marrow-derived macrophages under inflammatory stress
J Cell Physiol
Spinal cord injury (SCI) causes cell death and consequently the breakdown of axons and myelin. The accumulation of myelin debris at the lesion site induces inflammation and blocks axonal regeneration. Hematogenous macrop
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Record Fields
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- Reference Id
- 6305
- Evidence Id
- 22895
- Core Evidence Id
- 22895
- Source Reference Id
- 5880
- Herb2 Reference Id
- HBREF006677
- Subject Paper Key
- HBIN045592_34705285
- Pubmed Id
- 34705285
- Doi
- 10.1002/jcp.30619
- Paper Title
- Taurolithocholic acid but not tauroursodeoxycholic acid rescues phagocytosis activity of bone marrow-derived macrophages under inflammatory stress
- Paper Abstract
- Spinal cord injury (SCI) causes cell death and consequently the breakdown of axons and myelin. The accumulation of myelin debris at the lesion site induces inflammation and blocks axonal regeneration. Hematogenous macrophages contribute to the removal of myelin debris. In this study, we asked how the inflammatory state of macrophages affects their ability to phagocytose myelin. Bone marrow-derived macrophages (BMDM) and Raw264.7 cells were stimulated with lipopolysaccharides (LPS) or interferon gamma (IFNgamma), which induce inflammatory stress, and the endocytosis of myelin was examined. We found that activation of the TLR4-NFkappaB pathway reduced myelin uptake by BMDM, while IFNgamma-Jak/STAT1 signaling did not. Since bile acids regulate lipid metabolism and in some cases reduce inflammation, our second objective was to investigate whether myelin clearance could be improved with taurolithocholic acid (TLCA), tauroursodeoxycholic acid or hyodeoxycholic acid. In BMDM only TLCA rescued myelin phagocytosis, when this activity was suppressed by LPS. Inhibition of protein kinase A blocked the effect of TLCA, while an agonist of the farnesoid X receptor did not rescue phagocytosis, implicating TGR5-PKA signaling in the effect of TLCA. To shed light on the mechanism, we measured whether TLCA affected the expression of CD36, triggering receptor on myeloid cells-2 (TREM2), and Gas6, which are known to be involved in phagocytosis and affected by inflammatory stimuli. Concomitant with an increase in expression of tumour necrosis factor alpha, LPS reduced expression of TREM2 and Gas6 in BMDM, and TLCA significantly diminished this downregulation. These findings suggest that activation of bile acid receptors may be used to improve myelin clearance in neuropathologies.
- Journal
- J Cell Physiol
- Publish Year
- 2022
- Experiment Subject
- Experiment Type
- Cell Experiment
- Phenotype Related
- Spinal Cord Injury; Tumour; Neuropathologies
- Paper Title Cn
- Paper Title En
- Taurolithocholic acid but not tauroursodeoxycholic acid rescues phagocytosis activity of bone marrow-derived macrophages under inflammatory stress
- Bilingual Status
- semi_complete