IL-8 as a Potential Therapeutic Target for Periodontitis and Its Inhibition by Caffeic Acid Phenethyl Ester In Vitro

International Journal of Molecular Sciences

Kuo-Feng Tseng¹  Chang-Yu Lee²  Yung-Kai Huang³  Jie-Sian Wang⁴  Ping-Hsuan Tsai⁴  Ming-Yi Shen⁴ 

[1] Department of Biological Sciences and Technology, China Medical University, Taichung 40402, Taiwan;Department of Dentistry, Taipei Medical University Hospital, Taipei 110301, Taiwan;Department of Oral Hygiene, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan;Graduate Institute of Biomedical Sciences, College of Medicine, China Medical University, Taichung 40402, Taiwan;

关键词: interleukin-8;    oral microbiota;    caffeic acid phenethyl ester;    periodontitis;    THP-1 cell;   

DOI  :  10.3390/ijms22073641

来源: DOAJ

【 摘 要 】

Salivary levels of interleukin-8 (IL-8) are elevated in patients with periodontitis. Caffeic acid phenethyl ester (CAPE) improves the periodontal status in subjects. However, whether CAPE can reduce IL-8 expression is unclear. We collected saliva to determine proinflammatory cytokine levels and used subgingival calculus and surrounding tissues from patients with periodontitis for oral microbiota analysis via 16s ribosomal RNA gene sequencing. THP-1 cells were stimulated with sterile-filtered saliva from patients, and target gene/protein expression was assessed. IL-8 mRNA expression was analyzed in saliva-stimulated THP-1 cells treated with CAPE and the heme oxygenase-1 (HO-1) inhibitor tin-protoporphyrin (SnPP). In 72 symptomatic individuals, IL-8 was correlated with periodontal inflammation (bleeding on probing, r = 0.45; p < 0.001) and disease severity (bleeding on probing, r = 0.45; p < 0.001) but not with the four oral microbiota species tested. Reduced salivary IL-8 secretion was correlated with effective periodontitis treatment (r = 0.37, p = 0.0013). In THP-1 cells, saliva treatment induced high IL-8 expression and IKK2 and nuclear factor-κB (NF-κB) phosphorylation. However, the IKK inhibitor BMS-345541, NF-κB inhibitor BAY 11-7082, and CAPE attenuated saliva-induced IL-8 expression. CAPE induced HO-1 expression and inhibited IKK2, IκBα, and NF-κB phosphorylation. Blocking HO-1 decreased the anti-inflammatory activity of CAPE. The targeted suppression of IL-8 production using CAPE reduces inflammation and periodontitis.

【 授权许可】

Unknown