The protective role of curcumin in human dental pulp stem cells stimulated by lipopolysaccharide via inhibiting NF-κB p65 phosphorylation to suppress NLRP3 inflammasome activation

  • Clin Oral Investig. 2023 Feb 3. doi: 10.1007/s00784-023-04885-8.
Chunhua Lan  1  2 ,  Yueming Qian  1  2 ,  Yumin Wang  1  2 ,  Yuemin Chen  1  2 ,  Chensheng Lin  3 ,  Yanding Zhang  3 ,  Xiaojing Huang  4  5
Affiliations
  • 1. Fujian Key Laboratory of Oral Diseases & Fujian Provincial Engineering Research Center of Oral Biomaterial & Stomatological Key Lab of Fujian College and University, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, China.
  • 2. Institute of Stomatology & Research Center of Dental and Craniofacial Implants, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, China.
  • 3. Fujian Key Laboratory of Developmental and Neural Biology, College of Life Sciences, Fujian Normal University, Fuzhou, China.
  • 4. Fujian Key Laboratory of Oral Diseases & Fujian Provincial Engineering Research Center of Oral Biomaterial & Stomatological Key Lab of Fujian College and University, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, China. [email protected].
  • 5. Institute of Stomatology & Research Center of Dental and Craniofacial Implants, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, China. [email protected].
PMID: 36735089 DOI: 10.1007/s00784-023-04885-8
Abstract

Objectives: This study aims to investigate the anti-inflammatory effect of curcumin and underlying mechanisms regarding the modulation of the NOD-like Receptor pyrin domain containing 3 (NLRP3) inflammasome in human dental pulp stem cells (hDPSCs).

Materials and methods: The impact of curcumin on the viability of hDPSCs was evaluated. The effect of curcumin on the expression of IL-1β and NLRP3 in hDPSCs stimulated by lipopolysaccharide (LPS) was assessed. Then, LPS-primed hDPSCs were pre-treated with curcumin before ATP triggering NLRP3 inflammasome activation, and NLRP3 inflammasome-related mediators were assessed. The mechanism of curcumin inactivation of LPS plus ATP-induced inflammasome associated with NF-κB pathway was explored. The NF-κB pathway related pro-inflammatory mediators at mRNA and protein levels were evaluated. The expression of NF-κB p65 and phosphorylation p65 was visualized after curcumin or NF-κB Inhibitor administrating respectively in hDPSCs with an activated NLRP3 inflammasome. Statistical analysis was performed.

Results: While curcumin at the concentration of 0.5-5 μM showed no obvious impact on the viability of hDPSCs, it significantly decreased IL-1β and NLRP3 mRNA expression in LPS-induced hDPSCs in a dose-dependent manner. Curcumin significantly inhibited the LPS plus ATP-primed NLRP3 inflammasome activation in hDPSCs (NLRP3, ASC, Caspase-1, and IL-1β). Curcumin evidently attenuated the LPS plus ATP-induced expression of NF-κB pathway-related pro-inflammatory mediators (IL-6, IL-8, TNF-α, and COX-2). Furthermore, curcumin effectively reduced p65 phosphorylation, which acts as an NF-κB Inhibitor in hDPSCs with an activated NLRP3 inflammasome.

Conclusions: Curcumin pre-treatment may exert an anti-inflammatory role via inactivation of the NLRP3 inflammasome by inhibiting NF-κB p65 phosphorylation in cultured hDPSCs.

Clinical relevance: Curcumin may have therapeutic potential in pulp inflammation.

Keywords
Curcumin; Human dental pulp stem cells; NF-κB; NLRP3 inflammasome; Pulp inflammation.
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