Caffeic acid phenethyl ester attenuates lipopolysaccharide-stimulated proinflammatory responses in human gingival fibroblasts via NF-κB and PI3K/Akt signaling pathway.
Periodontal diseases often begin with chronic gingival inflammation, which causes the destruction of periodontal tissues. Inflammatory immune responses from host cells to bacteria, such as Porphyromonas gingivalis (P. gingivalis), cause periodontal degradation. Human gingival fibroblasts (HGFs) are the major cells in periodontal soft tissues. When stimulated by lipopolysaccharide (LPS), HGFs could secrete several pro-inflammatory cytokines and chemokines, such as interleukins (ILs) IL-6, IL-8, inducible nitric oxide synthase (iNOS), and cyclooxygenase 2 (COX-2). Caffeic acid phenethyl ester (CAPE) is the main active component of propolis, which is collected by honeybees from different plants and known for its anti-inflammatory effects. The anti-inflammatory effects of CAPE on the LPS-induced HGFs were demonstrated in this study. HGFs were pretreated with CAPE (10, 20, and 30µm) for 1h, followed by LPS stimulation (1μg/ml) for 24h. Enzyme-linked immunosorbent assay, Western blot analysis, and immunofluorescence staining were used to evaluate the production of IL-6, IL-8, iNOS, and COX-2, as well as the activation of TLR4-mediated NF-κB, PI3K/AKT, and MAPK signaling pathways. The results indicated that CAPE inhibits LPS-induced IL-6, IL-8, iNOS, and COX-2 production in a dose-dependent manner. Moreover, CAPE suppresses LPS-induced TLR4/MyD88 and nuclear factor kappa B (NF-κB) activation. In addition, phosphatidylinositol 3 kinase (PI3K) and protein kinase B (AKT) phosphorylation was inhibited by CAPE. These results demonstrated that CAPE could be effective for treating of periodontal diseases.
The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedical Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, People's Republic of China.
Lei
L
Li
The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedical Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, People's Republic of China.
Wei
W
Sun
The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedical Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, People's Republic of China.
Tao
T
Wu
The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedical Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, People's Republic of China.
Rui
R
Lu
The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedical Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, People's Republic of China. Electronic address: Shibin_dentist@126.com.
Bin
B
Shi
D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D002109:Caffeic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects* / Q000473:pathology*; D005786:Gene Expression Regulation / Q000187:drug effects; D005881:Gingiva / Q000473:pathology*; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D051996:Transcription Factor RelA / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D002109:Caffeic Acids; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D053594:Myeloid Differentiation Factor 88; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D051996:Transcription Factor RelA; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol
4′,6-diamidino-2-phenylindole (PubChemCID:2954); Caffeic acid phenethyl ester (CAPE); Dimethylsulfoxide (PubChemCID:679); Formaldehyde (PubChemCID: 712); Human gingival fibroblasts (HGFs); Lipopolysaccharide (LPS); Nuclear transcription factor-kappa B (NF-κB); Periodontal diseases; Sodium dodecyl sulfate (PubChemCID: 3423265); Triton X-100 (PubChemCID:5590); Tween 20 (PubChemCID:443314)