2. Academic Validation
  3. Inducing phospholipase A2 and cyclooxygenase-2 expression and prostaglandins' production of human dental pulp cells by activation of NOD receptor and its downstream signaling

Inducing phospholipase A2 and cyclooxygenase-2 expression and prostaglandins' production of human dental pulp cells by activation of NOD receptor and its downstream signaling

  • Int J Biol Macromol. 2025 Mar:292:139193. doi: 10.1016/j.ijbiomac.2024.139193.
Mei-Chi Chang 1,  Shu-Hui Chang 2,  Yi-Ling Tsai 3,  Yu-Hwa Pan 4,  Sin-Yuet Yeung 4,  Hsiao-Hua Chang 5,  Jiiang-Huei Jeng 6
Affiliations

Affiliations

  • 1 Biomedical Science Team, Chang Gung University of Science and Technology, Kwei-Shan, Taoyuan City, Taiwan; Department of Dentistry, Chang Gung Memorial Hospital, Taipei, Taiwan.
  • 2 School of Public Health, National Taiwan University, Taipei, Taiwan.
  • 3 School of Dentistry, National Taiwan University Medical College, Taipei, Taiwan; Department of Dentistry, National Taiwan University Hospital, Taipei, Taiwan.
  • 4 Department of Dentistry, Chang Gung Memorial Hospital, Taipei, Taiwan.
  • 5 School of Dentistry, National Taiwan University Medical College, Taipei, Taiwan; Department of Dentistry, National Taiwan University Hospital, Taipei, Taiwan. Electronic address: [email protected].
  • 6 School of Dentistry, National Taiwan University Medical College, Taipei, Taiwan; Department of Dentistry, National Taiwan University Hospital, Taipei, Taiwan; School of Dentistry, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Dentistry, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. Electronic address: [email protected].
PMID: 39730047 DOI: 10.1016/j.ijbiomac.2024.139193
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 E2 (PGE2) and PGF2α secretion in HDPCs. TriDAP activated TAK1, MEK/ERK, and p38 signaling. COX-2 expression, PGE2, and PGF2α 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 PGE2 and PGF2α 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.

Keywords

NOD1/NOD2 receptors; Pathogenic microorganisms; Prostaglandins; Pulpal inflammation; Pulpitis; Signal transduction.

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