Expression profiling of TRIM protein family in THP1-derived macrophages following TLR stimulation

Area of Science:

• Immunology
• Molecular Biology
• Genetics

Background:

• Activated macrophages are crucial in inflammatory diseases like septic shock and atherosclerosis.
• Understanding the molecular mechanisms that regulate macrophage activation is essential.
• The tripartite motif (TRIM) family has emerged as significant in innate immunity and antiviral responses.

Purpose of the Study:

• To systematically analyze the mRNA expression of TRIM molecules in human macrophages stimulated by various toll-like receptor (TLR) ligands.
• To identify novel TRIM genes regulated by TLR3 and TLR4 ligands.
• To investigate the role of TRIM59 in modulating macrophage activation.

Main Methods:

• Systematic analysis of mRNA expression of TRIM molecules in human THP1-derived macrophages.
• Activation of macrophages using different toll-like receptor (TLR) ligands.
• Confirmation of protein level changes using Western blot.
• Functional studies involving TRIM59 overexpression and siRNA-mediated knockdown.

Main Results:

• Twenty-nine TRIM members showed significant induction (>3 fold) by TLR ligands, with 19 belonging to the TRIM C-IV subgroup.
• A novel group of TRIM genes (TRIM14, 15, 31, 34, 43, 48, 49, 51, and 61) were identified as significantly upregulated by TLR3 and TLR4 ligands.
• TRIM59 expression was downregulated by TLR3 and TLR4 ligands in both human and mouse macrophages.
• Overexpression of TRIM59 suppressed LPS-induced macrophage activation, while TRIM59 knockdown enhanced it.

Conclusions:

• The study provides a comprehensive overview of TLR ligand-induced TRIM gene expression in macrophages.
• TRIM59 acts as a negative regulator of LPS-induced macrophage activation.
• These findings offer new insights into the role of TRIM proteins in regulating innate immune responses and inflammatory diseases.