Targeting TREM1: A Novel Therapeutic Approach to Mitigate Necrotizing Enterocolitis Injury in Murine Neonates

Necrotizing enterocolitis (NEC) is a severe gastrointestinal disease primarily affecting premature infants. The high mortality rate, ranging from 20-50%, mandates new therapeutic targets and treatment strategies. The present study demonstrates that TNBS (2,4,6-trinitrobenzenesulfonic acid) induced NEC-like injury is associated with the requirement of monocytes in the neonatal intestine with expressing TREM-1 (Triggering Receptor Expressed on Myeloid Cells-1). Consistent with the elevated expression of TREM-1 on monocytes, we notably found higher iFABP (intestinal fatty acid binding protein) expression, intestinal injury, and elevated inflammatory cytokines. Similarly, surgically removed intestinal specimens from human patients with NEC, we found CD14+ monocytes co-localized with TREM-1. Inhibition of TREM-1 by LP17 (LQVTDSGLYRCVIYHPP, an inhibitory peptide), in lipopolysaccharide-treated murine macrophage (RAW 264.7) cells showed decreased inflammatory cytokine production when compared to the vehicle controls. Furthermore, the administration of LP17 to NEC-like injured mice was found to reduce the intestinal injury, inflammatory response, and improve survival by inhibiting TREM1. These findings provide valuable information that TREM-1 could constitute a new therapeutic target during NEC.