CORM-2 prevents human gingival fibroblasts from lipoteichoic acid-induced VCAM-1 and ICAM-1 expression by inhibiting TLR2/MyD88/TRAF6/PI3K/Akt/ROS/NF-κB signaling pathway.

Abstract

Periodontal diseases are prevalent worldwide. Lipoteichoic acid (LTA), a major component of gram-positive bacteria, may play a key role in periodontally inflammatory diseases. Carbon monoxide (CO) is a critical messenger in many biological processes. It can elicit various biological properties, especially anti-inflammatory effects. As the straight administration of CO remains difficult, CO-releasing molecules (CO-RMs) are emerging as promising alternatives. To explore the pharmacological actions and signaling pathways of CO battling LTA-induced periodontal inflammation, this study investigated the cytoprotective effects of CORM-2 against the adhesion of THP-1 monocytes to human gingival fibroblasts (HGFs) and the underlying molecular mechanism. After exposing HGFs to LTA with or without CORM-2 pretreatment, monocyte adhesion was determined. VCAM-1 and ICAM-1 expression in HGFs was measured by real-time PCR. To identify the signaling pathways of CO involved in the cytoprotective effects of CORM-2, HGFs underwent pharmacological or genetical interventions before LTA incubation. The expression and/or activity of possible regulatory molecules were determined. The release of pro-inflammatory cytokines, including IL-1β, IL-6, and TNF-α, were measured using ELISA. The results showed that LTA increased cytokine production and upregulated VCAM-1 and ICAM-1 expression in HGFs, promoting monocyte adhesion. These events were dependent on TLR2/MyD88/TRAF6- and PI3K/Akt/NADPH oxidase/ROS-regulated NF-κB activation. CORM-2 inhibited LTA-induced inflammatory cascades in HGFs, in which CO seemed to be the hitman. To conclude, CO released from CORM-2 can prevent the LTA-stimulated HGFs from increasing VCAM-1 and ICAM-1 expression and promoting monocyte adhesion by inhibiting TLR2/MyD88/TRAF6 association and PI3K/Akt/NADPH oxidase/ROS signaling, both converge on the canonical NF-κB activation.

• Authors: Ching-Yi Cheng, Yu-Hsu Chen, Thi Thuy Tien Vo, Ying Chui Hong, Ching-Shuen Wang, Quang Canh Vo, Han-Chin Chou, Ting-Wei Huang, I-Ta Lee
• Journal: Biochemical pharmacology (Biochem Pharmacol) Vol. 201 Pg. 115099 (07 2022) ISSN: 1873-2968 [Electronic] England
• PMID: 35617999 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 Elsevier Inc. All rights reserved.

Chemical References

• Lipopolysaccharides
• MYD88 protein, human
• Myeloid Differentiation Factor 88
• NF-kappa B
• Organometallic Compounds
• Reactive Oxygen Species
• TLR2 protein, human
• TNF Receptor-Associated Factor 6
• Teichoic Acids
• Toll-Like Receptor 2
• Vascular Cell Adhesion Molecule-1
• tricarbonyldichlororuthenium (II) dimer
• Intercellular Adhesion Molecule-1
• lipoteichoic acid
• NADPH Oxidases
• Proto-Oncogene Proteins c-akt

Topics

• Fibroblasts
• Humans
• Intercellular Adhesion Molecule-1 (genetics, metabolism)
• Lipopolysaccharides
• Myeloid Differentiation Factor 88 (metabolism)
• NADPH Oxidases (metabolism)
• NF-kappa B (metabolism)
• Organometallic Compounds (pharmacology)
• Phosphatidylinositol 3-Kinases (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Reactive Oxygen Species (metabolism)
• Signal Transduction
• TNF Receptor-Associated Factor 6 (metabolism)
• Teichoic Acids
• Toll-Like Receptor 2 (genetics, metabolism)
• Vascular Cell Adhesion Molecule-1 (genetics, metabolism)