Amplification by (-)-epigallocatechin gallate and chlorogenic acid of TNF-α-stimulated interleukin-6 synthesis in osteoblasts.
Polyphenolic compounds in foods and beverages have beneficial effects on human health. (-)-Epigallocatechin gallate (EGCG) and chlorogenic acid (CGA), a major flavonoid in green tea and a major phenolic acid in coffee, respectively, have potent properties, including antioxidative effects. Our previous study demonstrated that p70 S6 kinase acts as a negative regulator in tumor necrosis factor-α (TNF-α)-stimulated interleukin-6 synthesis in osteoblast-like MC3T3-E1 cells. In the present study, the effects of EGCG and CGA on the TNF-α-stimulated interleukin‑6 synthesis were investigated in MC3T3‑E1 cells. EGCG and CGA significantly enhanced TNF-α-stimulated interleukin-6 release. In addition, the interleukin-6 mRNA expression levels induced by TNF‑α were supported by EGCG, as well as CGA. EGCG markedly attenuated the TNF-α-induced phosphorylation of p70 S6 kinase whereas CGA failed to affect the phosphorylation. These results strongly suggest that EGCG and CGA enhance the TNF-α-stimulated interleukin-6 synthesis in osteoblasts, and that the amplifying effect of EGCG, but not CGA, is exerted via inhibiting p70 S6 kinase.
Department of Orthopedic Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya 467‑8601, Japan.
Naohiro
N
Yamamoto
Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu 501‑1194, Japan.
Haruhiko
H
Tokuda
Department of Orthopedic Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya 467‑8601, Japan.
Gen
G
Kuroyanagi
Department of Orthopedic Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya 467‑8601, Japan.
Shingo
S
Kainuma
Department of Orthopedic Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya 467‑8601, Japan.
Reou
R
Ohguchi
Department of Orthopedic Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya 467‑8601, Japan.
Kazuhiko
K
Fujita
Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu 501‑1194, Japan.
Rie
R
Matsushima-Nishiwaki
Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu 501‑1194, Japan.
Osamu
O
Kozawa
Department of Orthopedic Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya 467‑8601, Japan.
Takanobu
T
Otsuka
D000818:Animals; D015153:Blotting, Western; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002460:Cell Line; D002726:Chlorogenic Acid / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation / Q000187:drug effects*; D015850:Interleukin-6 / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D002726:Chlorogenic Acid; D002392:Catechin; C045651:epigallocatechin gallate; D038762:Ribosomal Protein S6 Kinases, 70-kDa