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

• DOI: 10.1007/s10753-013-9732-x
• Publication Date: 2013-09-21T05:53:25Z
• Authors: Dejie Liang; Fengyang Li; Yunhe Fu; Yongguo Cao; Xiaojing Song; Tiancheng Wang; Wei Wang; Mengyao Guo; Ershun Zhou; Depeng Li; Zhengtao Yang; Naisheng Zhang
• Keywords: Inflammation; Lipopolysaccharides; 0301 basic medicine; Cell Survival; Interleukin-6; MAP Kinase Signaling System; Macrophages; Interleukin-1beta; Anti-Inflammatory Agents; JNK Mitogen-Activated Protein Kinases; Down-Regulation; Epithelial Cells; Mastitis; 3. Good health; 03 medical and health sciences; Mammary Glands, Animal; Anti-Infective Agents; Cyclooxygenase 2; Animals; Female; I-kappa B Proteins; Extracellular Signal-Regulated MAP Kinases; Cells, Cultured

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.