TY - JOUR
T1 - Surfactin reduces particulate matter–induced VCAM-1–dependent monocyte adhesion in human gingival fibroblasts by increasing Nrf2-dependent HO-1 expression
AU - Vo, Thi Thuy Tien
AU - Huang, Han Wei
AU - Wee, Yinshen
AU - Feng, Sheng Wei
AU - Cheng, Hsin Chung
AU - Tuan, Vo Phuoc
AU - Lee, I. Ta
N1 - Funding Information:
This work was supported by the Taipei Medical University Hospital, grant number 110TMUH‐NE‐03.
Publisher Copyright:
© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
PY - 2022/1
Y1 - 2022/1
N2 - Background and objectives: The mechanisms of particulate matter (PM) toxicity involve the generation of ROS and upregulation of proinflammatory molecules. Nrf2 is a multifunctional cytoprotective transcription factor that regulates the expression of various antioxidant, anti-inflammatory, and detoxifying molecules, such as HO-1. As surfactin has potential to induce Nrf2 activation and HO-1 expression, this study aimed to investigate the anti-inflammatory effects of surfactin on PM-exposed human gingival fibroblasts (HGFs) and signaling pathways engaged by surfactin. Materials and methods: Human gingival fibroblasts were challenged by PM with or without surfactin pretreatment. The expression of Nrf2, HO-1, VCAM-1, and other molecules was determined by western blot, real-time PCR, or ELISA. Human monocytic THP-1 cells labeled with fluorescent reagent were added to HGFs, and the cell adhesion was assessed. ROS generation and NADPH oxidase activity were also measured. The involvement of Nrf2/HO-1 and ROS signaling pathways was investigated by treating HGFs with specific pathway interventions, genetically or pharmacologically. One dose of surfactin was given to mice before PM treatment to explore its in vivo effect on VCAM-1 expression in gingival tissues. Results: Particulate matter led to VCAM-1–dependent monocyte adhesion in HGFs, which was regulated by PKCα/NADPH oxidase/ROS/STAT1/IL-6 pathway. Surfactin could attenuate monocyte adhesion by disrupting this VCAM-1–dependent pathway. Additionally, surfactin promoted Nrf2-dependent HO-1 expression in HGFs, mitigating VCAM-1 expression. PM-treated mice exhibited the lower expression of IL-6 and VCAM-1 in gingival tissues if they previously received surfactin. Conclusion: Surfactin exerts anti-inflammatory effects against PM-induced inflammatory responses in HGFs by inhibiting VCAM-1–dependent pathway and inducing Nrf2/HO-1 axis.
AB - Background and objectives: The mechanisms of particulate matter (PM) toxicity involve the generation of ROS and upregulation of proinflammatory molecules. Nrf2 is a multifunctional cytoprotective transcription factor that regulates the expression of various antioxidant, anti-inflammatory, and detoxifying molecules, such as HO-1. As surfactin has potential to induce Nrf2 activation and HO-1 expression, this study aimed to investigate the anti-inflammatory effects of surfactin on PM-exposed human gingival fibroblasts (HGFs) and signaling pathways engaged by surfactin. Materials and methods: Human gingival fibroblasts were challenged by PM with or without surfactin pretreatment. The expression of Nrf2, HO-1, VCAM-1, and other molecules was determined by western blot, real-time PCR, or ELISA. Human monocytic THP-1 cells labeled with fluorescent reagent were added to HGFs, and the cell adhesion was assessed. ROS generation and NADPH oxidase activity were also measured. The involvement of Nrf2/HO-1 and ROS signaling pathways was investigated by treating HGFs with specific pathway interventions, genetically or pharmacologically. One dose of surfactin was given to mice before PM treatment to explore its in vivo effect on VCAM-1 expression in gingival tissues. Results: Particulate matter led to VCAM-1–dependent monocyte adhesion in HGFs, which was regulated by PKCα/NADPH oxidase/ROS/STAT1/IL-6 pathway. Surfactin could attenuate monocyte adhesion by disrupting this VCAM-1–dependent pathway. Additionally, surfactin promoted Nrf2-dependent HO-1 expression in HGFs, mitigating VCAM-1 expression. PM-treated mice exhibited the lower expression of IL-6 and VCAM-1 in gingival tissues if they previously received surfactin. Conclusion: Surfactin exerts anti-inflammatory effects against PM-induced inflammatory responses in HGFs by inhibiting VCAM-1–dependent pathway and inducing Nrf2/HO-1 axis.
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U2 - 10.1111/jre.12944
DO - 10.1111/jre.12944
M3 - Article
C2 - 34716926
AN - SCOPUS:85118386523
SN - 0022-3484
VL - 57
SP - 115
EP - 130
JO - Journal of Periodontal Research
JF - Journal of Periodontal Research
IS - 1
ER -