Dental caries with invasion and infection by microorganisms may induce pulpitis and intolerable pain. L-Ala-γ-D-Glu-mDAP (TriDAP) is a DAP-comprising muramyl tripeptide and a peptidoglycan degradation product found in gram-negative pulpal pathogens. TriDAP activates nucleotide-binding oligomerization domain1/2 (NOD1/NOD2) and induces tissue inflammatory responses. This study aimed to test whether TriDAP stimulates cytosolic phospholipase A2 (cPLA2), cyclooxygenase-2 (COX-2), and prostanoid production in human dental pulp cells (HDPCs) and their inhibition by signal transduction inhibitors, melatonin, and eugenol. We found that TriDAP stimulated cPLA2 and COX-2 expression as well as prostaglandin E