Zhong Jing, Shi Qi-Qing, Zhu Min-Min, Shen Jian, Wang Hui-Hui, Ma Duan, Miao Chang-Hong
Department of Anesthesiology, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Children's Hospital of Fudan University, Shanghai, China.
PLoS One. 2015 Nov 24;10(11):e0143662. doi: 10.1371/journal.pone.0143662. eCollection 2015.
Malignant fibrous histiocytoma amplified sequence 1 (MFHAS1) has a potential immunoregulatory role dependent on Toll-like receptors (TLRs). TLR2, associated with deleterious systemic inflammation, cardiac dysfunction, and acute kidney injury, acts synergistically in sepsis. The role of MFHAS1 in targeting TLR2 involved in sepsis has not been examined thus far. This study aimed to examine the relationship of MFHAS1 and sepsis, and the effect of MFHAS1 on the TLR2 signaling pathway. Blood samples were collected from eight sepsis patients after surgery and eight patients undergoing selective surgery to determine blood MFHAS1 levels. HEK 293 cells, RAW 264.7 macrophages and THP-1 monocytes were used to confirm the effect of MFHAS1 on TLR2 signaling pathway. Our study showed that blood MFHAS1 was significantly elevated in septic patients, and MFHAS1 was more increased in mononuclear cells from septic patients. Pam3CSK4 (TLR2 ligand) was found to induce MFHAS1 production in RAW 264.7 murine macrophages and THP-1 human monocytes in a time-dependent manner. MFHAS1 has dual effects on TLR2 signaling pathway and inflammation, i.e., inhibitory effect at 6 hours, and then stimulatory effect after 24 hours through the activation of TLR2/NF-κB signaling pathway, and MFHAS1 induced the phosphorylation of JNK and p38 after TLR2 stimulation.
恶性纤维组织细胞瘤扩增序列1（MFHAS1）具有依赖于Toll样受体（TLR）的潜在免疫调节作用。与有害的全身炎症、心脏功能障碍和急性肾损伤相关的TLR2在脓毒症中起协同作用。迄今为止，尚未研究MFHAS1在靶向参与脓毒症的TLR2中的作用。本研究旨在探讨MFHAS1与脓毒症的关系，以及MFHAS1对TLR2信号通路的影响。收集8例脓毒症患者术后及8例接受选择性手术患者的血样，以测定血液中MFHAS1水平。使用HEK 293细胞、RAW 264.7巨噬细胞和THP-1单核细胞来证实MFHAS1对TLR2信号通路的影响。我们的研究表明，脓毒症患者血液中MFHAS1显著升高，脓毒症患者单核细胞中MFHAS1升高更明显。发现Pam3CSK4（TLR2配体）能以时间依赖性方式诱导RAW 264.7小鼠巨噬细胞和THP-1人单核细胞产生MFHAS1。MFHAS1对TLR2信号通路和炎症具有双重作用，即在6小时时具有抑制作用，然后在24小时后通过激活TLR2/NF-κB信号通路产生刺激作用，并且MFHAS1在TLR2刺激后诱导JNK和p38磷酸化。
