Soluble triggering receptor expressed on myeloid cells-1 as a new therapeutic molecule in rheumatoid arthritis

Abstract

Triggering receptor expressed on myeloid cells-1 (TREM-1) is a recently identified cell surface receptor that is expressed mainly on monocytes and neutrophils, and plays an important role as an amplifier of inflammatory response in acute and chronic inflammatory conditions. Recent studies suggested that TREM-1 contributes to the pathogenesis of rheumatoid arthritis (RA) and therefore TREM-1 could be a new therapeutic target in RA. In addition to its membrane-bound form, a soluble form of TREM-1 (sTREM-1) exists that is liberated by the proteolytic cleavage of membrane-bound form. This soluble form works as decoy receptor to prevent the binding of its ligand to membrane-bound TREM-1 and to inhibit the effect of TREM-1 activation. Proteolytic cleavage of TNF receptor (TNFR) has been reported and soluble TNFR are capable of binding and neutralizing TNF, thus working as natural TNF antagonist. Currently, etanercept, a soluble TNF-receptor fusion protein has been widely used to treat RA. In this report, we suggest that sTREM-1 can be used as a new therapeutic molecule in RA.