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. 2024 Jul 22:17:4845-4863.
doi: 10.2147/JIR.S460954. eCollection 2024.

CORM-3 Inhibits the Inflammatory Response of Human Periodontal Ligament Fibroblasts Stimulated by LPS and High Glucose

Haoyang Tian #  1 , Hui Chen #  2 , Xiaochun Yin  2 , Meiyi Lv  3 , Lingling Wei  1 , Yuna Zhang  4 , Shuhan Jia  5 , Jingyuan Li  1 , Hui Song  1
Affiliations

CORM-3 Inhibits the Inflammatory Response of Human Periodontal Ligament Fibroblasts Stimulated by LPS and High Glucose

Haoyang Tian et al. J Inflamm Res. .

Abstract

Introduction: Diabetes has been recognized as an independent risk factor for periodontitis. Increasing evidences indicate that hyperglycemia aggravates inflammatory response of human periodontal ligament cells (hPDLCs). Carbon monoxide-releasing molecule-3 (CORM-3) is a water-soluble compound that can release carbon monoxide (CO) in a controllable manner. CORM-3 has been shown the anti-inflammatory effect in different cell lineages.

Methods: We stimulated periodontal ligament cells with LPS and high glucose. The expression of inflammatory cytokine was detected by ELISA. RT-qPCR, Western blot and immunofluorescence were used to detect the expression of TLR2, TLR4, RAGE and the activation of NF-κB pathway. We performed silencing and overexpression treatment of RAGE targeting the role of RAGE. We performed the immunostaining of paraffin sections of the periodontitis model in diabetes rats.

Results: The results showed that CORM-3 significantly inhibited the expression of inflammatory cytokine in hPDLCs stimulated with LPS and high glucose. CORM-3 also inhibited LPS and high glucose-induced expression of RAGE/NF-κB pathway and TLR2/TLR4/NF-κB pathway. Silence of RAGE resulted in significantly decreased expression of proteins above. Overexpression of RAGE significantly enhanced the expression of these factors. CORM-3 abrogated the effect of RAGE partially. In animal model, CORM-3 suppressed the inflammatory response of periodontal tissues in experimental periodontitis of diabetic rats.

Discussion: Our research proved CORM-3 reduced the inflammatory response via RAGE/NF-κB pathway and TLR2/TLR4/NF-κB pathway in the process of high glucose exacerbated periodontitis. These findings demonstrated the role of RAGE in the process of high glucose exacerbated periodontitis and suggested that CORM3 be a potential therapeutic strategy for the treatment of diabetes patients with periodontitis.

Keywords: carbon monoxide-releasing molecules; diabetes; lipopolysaccharide; periodontitis; receptor for advanced glycation end products.

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Conflict of interest statement

The authors declare no conflicts of interest in this work.

Figures

None
Graphical abstract
Figure 1
Figure 1
CORM-3 reduces LPS-induced release of inflammatory cytokines from hPDLCs in the presence of high glucose.
Figure 2
Figure 2
CORM-3 reduces LPS-induced TLR-2 and TLR-4 expression in hPDLCs in the presence of high‐glucose.
Figure 3
Figure 3
CORM-3 reduces high‐glucose-promoted RAGE expression and NF-κB pathway activation in LPS-induced hPDLCs.
Figure 4
Figure 4
The modulatory effect of CORM-3 on the expression of TLR2 and TLR4 and NF-κB pathway-related factors after RAGE silencing.
Figure 5
Figure 5
CORM-3 reduces the expression of receptors and pathway-related molecules after RAGE overexpression.
Figure 6
Figure 6
CORM-3 suppresses the inflammatory response in experimental periodontitis of diabetic rats.
Figure 7
Figure 7
CORM-3 reduced the expression of RAGE and NFκB-p65 in experimental periodontitis of diabetic rats.
See this image and copyright information in PMC

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