Thymol Inhibits LPS-Stimulated Inflammatory Response via Down-Regulation of NF-κB and MAPK Signaling Pathways in Mouse Mammary Epithelial Cells

• Published in: Inflammation 2014-02, Vol.37 (1), p.214-222
• Main Authors: Liang, Dejie, Li, Fengyang, Fu, Yunhe, Cao, Yongguo, Song, Xiaojing, Wang, Tiancheng, Wang, Wei, Guo, Mengyao, Zhou, Ershun, Li, Depeng, Yang, Zhengtao, Zhang, Naisheng
• Format: Article
• Language: English
• Subjects: Animals; Anti-Infective Agents - pharmacology; Anti-inflammatory agents; Anti-Inflammatory Agents - pharmacology; Biomedicine; c-Jun protein; Cell culture; Cell Survival - drug effects; Cells, Cultured; Cyclooxygenase 2 - analysis; Cyclooxygenase-2; Dosage; Down-Regulation; Enzyme-linked immunosorbent assay; Epithelial cells; Epithelial Cells - immunology; Extracellular signal-regulated kinase; Extracellular Signal-Regulated MAP Kinases - metabolism; Female; I-kappa B Proteins - metabolism; IL-1β; Immunology; Inflammation; Inflammation - chemically induced; Inflammation - drug therapy; Inflammation - immunology; Interleukin 6; Interleukin-1beta - analysis; Interleukin-6 - analysis; Interleukin-6 - biosynthesis; Internal Medicine; JNK Mitogen-Activated Protein Kinases - metabolism; JNK protein; Kinases; Lipopolysaccharides; Macrophages - metabolism; Mammary gland; Mammary Glands, Animal - cytology; Mammary Glands, Animal - immunology; MAP kinase; MAP Kinase Signaling System - drug effects; Mastitis; Mastitis - drug therapy; Mice; Mice, Inbred BALB C; NF-KappaB Inhibitor alpha; NF-κB protein; Nitric oxide; Nitric Oxide Synthase Type II; Nitric-oxide synthase; Origanum; p38 Mitogen-Activated Protein Kinases - metabolism; Pathology; Pharmacology/Toxicology; Phosphorylation; Protein kinase; Proteins; Rheumatology; Signal transduction; Thymol; Thymol - pharmacology; Thymus; Transcription Factor RelA - biosynthesis; Transcription Factor RelA - metabolism; Transcription factors; Tumor Necrosis Factor-alpha - analysis; Tumor Necrosis Factor-alpha - biosynthesis; Tumor necrosis factor-TNF; Tumor necrosis factor-α
• ISSN: 0360-3997; 1573-2576
• DOI: 10.1007/s10753-013-9732-x

Thymol is a natural monoterpene phenol primarily found in thyme, oregano, and tangerine peel . It has been shown to possess anti-inflammatory property both in vivo and in vitro . In the present paper, we studied the anti-inflammatory effect of thymol in lipopolysaccharide (LPS)-stimulated mouse mammary epithelial cells (mMECs). The mMECs were stimulated with LPS in the presence or absence of thymol (10, 20, 40 μg/mL). The concentrations of tumor necrosis factor α (TNF-α), interleukin (IL)-6, and IL-1β in the supernatants of culture were determined using enzyme-linked immunosorbent assay. Cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), extracellular signal-regulated protein kinase (ERK), c-Jun N-terminal kinase (JNK), nuclear factor-κB (NF-κB), and inhibitor protein of NF-κB (IκBα) were measured using western blot. The results showed that thymol markedly inhibited the production of TNF-α and IL-6 in LPS-stimulated mMECs. The expression of iNOS and COX-2 was also suppressed by thymol in a dose-dependent manner. Furthermore, thymol blocked the phosphorylation of IκBα, NF-κB p65, ERK, JNK, and p38 mitogen-activated protein kinases (MAPKs) in LPS-stimulated mMECs. These results indicate that thymol exerted anti-inflammatory property in LPS-stimulated mMECs by interfering the activation of NF-κB and MAPK signaling pathways. Thereby, thymol may be a potential therapeutic agent against mastitis.