Blockade of CD354 (TREM-1) Ameliorates Anti-GBM-Induced Nephritis.

Abstract

CD354, Triggering Receptor of Myeloid Cells-1 (TREM-1), is a potent amplifier of myeloid immune responses. Our goal was to determine the expression and function of TREM-1 in immune-mediated nephritis. An anti-glomerular basement membrane antibody (anti-GBM)-induced nephritis model was employed, where mice were sensitized with rabbit IgG followed by anti-GBM serum to induce disease. Anti-GBM-treated 129x1/svJ mice developed severe nephritis whereas C57BL/6 (B6) mice were resistant to disease. Anti-GBM disease resulted in elevated renal TREM-1 messenger RNA (mRNA) and protein levels and increased urine TREM-1 levels in 129x1/svJ. TREM-1 blockade with an inhibitory peptide, LP17, inhibited proteinuria and renal disease as measured by glomerulonephritis class, severity of tubulointerstitial disease, crescent formation, and inflammatory cell infiltrates. In sum, TREM-1 is upregulated in renal inflammation and plays a vital role in driving disease. Thus, TREM-1 blockade emerges as a potential therapeutic avenue for immune-mediated renal diseases such as lupus nephritis.

• Authors: Yong Du, Tianfu Wu, Xin J Zhou, Laurie S Davis, Chandra Mohan
• Journal: Inflammation (Inflammation) Vol. 39 Issue 3 Pg. 1169-76 (Jun 2016) ISSN: 1573-2576 [Electronic] United States
• PMID: 27083877 (Publication Type: Journal Article)

Chemical References

• Autoantibodies
• Membrane Glycoproteins
• RNA, Messenger
• Receptors, Immunologic
• TREM1 protein, mouse
• Triggering Receptor Expressed on Myeloid Cells-1
• antiglomerular basement membrane antibody

Topics

• Animals
• Autoantibodies (pharmacology)
• Disease Models, Animal
• Lupus Nephritis (chemically induced, metabolism)
• Membrane Glycoproteins (analysis, antagonists & inhibitors, genetics)
• Mice
• Mice, Inbred Strains
• RNA, Messenger (biosynthesis)
• Rabbits
• Receptors, Immunologic (analysis, antagonists & inhibitors, genetics)
• Triggering Receptor Expressed on Myeloid Cells-1
• Up-Regulation