TREM-2 negatively regulates LPS-mediated inflammatory response in rat bone marrow-derived MSCs

Area of Science:

• Immunology
• Stem Cell Biology
• Molecular Biology

Background:

• Previous studies identified Triggering Receptor Expressed on Myeloid Cells 2 (TREM-2) in human mesenchymal stem cells (MSCs).
• The specific role of TREM-2 in regulating inflammation within MSCs remained unclear.
• Investigating TREM-2's function in rat bone marrow MSCs is crucial for understanding its immune regulatory potential.

Purpose of the Study:

• To elucidate the immune regulatory function of TREM-2 in rat bone marrow MSCs.
• To explore the underlying molecular mechanisms by which TREM-2 influences inflammatory responses.
• To determine if TREM-2 can be a target for modulating MSC-mediated immunity.

Main Methods:

• TREM-2 expression was established in rat MSCs at both mRNA and protein levels using lentiviral vectors.
• MSCs were stimulated with lipopolysaccharide (LPS) to induce an inflammatory response.
• Gene transcription levels of TREM-2 and inflammatory cytokines were analyzed.
• Protein expression of inflammatory cytokines (TNF-α, IL-1β, IL-10) and downstream signaling molecules (AKT, p38 MAPK) was assessed via Western blot.

Main Results:

• LPS stimulation increased TREM-2 and inflammatory cytokine gene transcription in MSCs.
• Overexpression of TREM-2 in MSCs significantly downregulated pro-inflammatory cytokines (TNF-α, IL-1β) and upregulated the anti-inflammatory cytokine IL-10.
• TREM-2 was found to downregulate LPS-induced inflammation by modulating the AKT and p38 MAPK signaling pathways.

Conclusions:

• TREM-2 acts as a negative regulator of the lipopolysaccharide-mediated inflammatory response in rat MSCs.
• The findings suggest TREM-2 plays a significant role in immune modulation within MSCs.
• TREM-2 represents a potential therapeutic target for immune regulation in the context of MSC-based therapies.