5-Methoxytryptophan Plays Critical Role in Suppressing LPS/TLR4-Mediating Inflammatory Response

• Main Authors: Chien-Chih Cheng, 鄭建志
• Other Authors: Cheng-Chin Kuo
• Format: Others
• Language: zh-TW
• Published: 2013
• Online Access: http://ndltd.ncl.edu.tw/handle/34894934238920810796

碩士 === 國防醫學院 === 生物化學研究所 === 101 === Inflammation is caused by excessive and inappropriate innate immune system activity such as an overwhelming activation of COX-2 and Toll-like receptors (TLRs)-signaling; the process has been linked to development of diseases and medical events, such as cancer and sepsis. TLRs play a critical role in regulating immune response and maintaining immune homeostasis. Furthermore, activation of TLR signaling by pathogen component and endogenous molecular is thought to be one mechanism initiating and driving systemic inflammation. We previously used comparative metabolomics approach to identify a novel tryptophan metabolite, 5-methoxytryptophan (5-MTP) which blocked cancer cell COX-2 expression induced by proinflammatory mediated in vitro and suppressed cancer growth and metastasis in vivo. Since LPS also active COX-2 expression to modulate inflammatory response, my these work focused on determining the involvement of 5-MTP in LPS/TLR4-mediated inflammation in vitro and in vitro. Experimentally, mouse macrophage cell line “RAW264.7” was used in vitro. RAW264.7 cells were treated with or without different concentration of 5-MTP. ELISA assay indicated that 5-MTP dose-dependently inhibited LPS induced level of IL-6 and TNF-Moreover, COX-2 expression induced LPS also was suppressed by 5-MTP . Macrophage cellular function plays a critical role in mediating the progression of inflammation disease, we thus evaluated the protective role of 5-MTP in LPS-induced inflammation animal models such as sepsis which is a potentially life-threatening complication of an infection. Notably, animal studies indicated that 5-MTP suppressed septic syndrome, including cytokine storm, coagulation abnormalities and lung damage, thereby leading to protect mice against LPS-induced lethal endotoxemia. Our findings suggest that 5-MTP will be of great value for developing new therapeutic strategies combining anti-inflammation and target therapies for treating sepsis and immune related disease.