Inducing phospholipase A2 and cyclooxygenase-2 expression and prostaglandins' production of human dental pulp cells by activation of NOD receptor and its downstream signaling.
Journal
International journal of biological macromolecules
Journal Volume
292
ISSN
1879-0003
Date Issued
2025-03
Author(s)
Chang, Mei-Chi
Chang, Shu-Hui
Pan, Yu-Hwa
Yeung, Sin-Yuet
Abstract
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 (PGE) and PGF secretion in HDPCs. TriDAP activated TAK1, MEK/ERK, and p38 signaling. COX-2 expression, PGE, and PGF production induced by TriDAP were prevented by 5Z-7oxozeaenol, SB203580, and U0126. Moreover ASB14780 (a cPLA2 inhibitor) and the clinical drugs melatonin and eugenol suppressed TriDAP- and Poly(I:C)-stimulated PGE and PGF production. These results indicate that NOD activation in HDPCs may stimulate COX-2 expression and prostaglandin production, which are crucial in pulpal inflammatory and repair responses. The effects of TriDAP and Poly(I:C) were associated with TAK1, p38, MEK/ERK, and cPLA2 in pulpal inflammation. PLA2 inhibitors, melatonin, and eugenol can be used to control pulpal inflammation associated with NOD1/2 and TLR3 activation.
Subjects
NOD1/NOD2 receptors
Pathogenic microorganisms
Prostaglandins
Pulpal inflammation
Pulpitis
Signal transduction
SDGs
Type
journal article