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

Abstract

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.

Clinical Significance of Inflammatory Factors, Osteocalcin, and Matrix Metalloproteinase-8 in Gingival Crevicular Fluid in Drug Treatment of Severe Periodontitis

“…At the same time, they also stimulate the host and activation of in ammatory cells and immune cells, which triggered systemic in ammation and immune response, leading to upregulation of in ammatory mediators' level and acute phase proteins level [12]. Il-6, IL-1β, and IL-8 were all in ammatory mediators that regulated the immune response in the host body to microbial infection and played a central role in the destruction of periodontal tissues [13][14][15]. In ammatory indicators such as IL-6, IL-1β, and IL-8 with an abnormal upward trend would aggravate the injury degree of vascular endothelial cells and further aggravate the in ammatory response of periodontal tissues, which may reduce the e ect of drug treatment and increase the risk of treatment failure.…”

Application of Ginsenoside Rd in Periodontitis With Inhibitory Effects on Pathogenicity, Inflammation, and Bone Resorption

“…Facing the challenge from bacteria, inflammatory cytokines such as IL-1β, IL-6 and IL-8 will be released by periodontal tissue cells and immunocytes, and these cytokines play important roles in the process of tissue destruction ( Pan et al., 2019 ; Huang et al., 2021 ). The anti-inflammatory effect of Rd has been demonstrated in other inflammatory diseases ( Liu et al., 2018 ; Yang et al., 2020 ) but rarely discussed in periodontitis.…”

Gene Set Enrichment Analysis and Ingenuity Pathway Analysis to verify the impact on Wnt Signaling Pathway in Taodan Granules Treated Psoriasis

“…The results indicated that TDGs contained Rutin, Caffeic acid, Cryptotanshinone, Tanshinone IIA, Formononetin, Liquiritin, Danshensu, and other active ingredients. Tanshinone IIA, Cryptotanshinone, and Danshensu are the three main bioactive components of Salvia miltiorrhiza Bunge, while all of them has proved to alleviate psoriasis [12,[20][21][22]. Formononetin proved to has strong anti-proliferation properties [23].…”