Involvement of TLR2 and TLR9 in the anti-inflammatory effects of chlorogenic acid in HSV-1-infected microglia.
OBJECTIVE
There is no effective medication to date for herpes simplex virus encephalitis (HSE). In this study, we investigated the anti-inflammatory effect of chlorogenic acid (CGA) on herpes simplex virus (HSV)-1-induced responses in BV2 microglia.


METHODS
The cellular model was established with BV2 cells stimulated by HSV-1 and then treated with CGA at different concentrations. Cell viability was assayed by the MTT assay. The mRNA expression of Toll-like receptor (TLR)-2, TLR9 and myeloid differentiation factor88 (Myd88) was assayed by real-time quantitative PCR, and the protein expression was assayed by flow cytometry or Western blotting. Tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 were measured by ELISA as well as real-time quantitative PCR. Nuclear NF-κB p65 protein was assayed by Western blotting.


RESULTS
The cell survival rate was significantly improved after CGA treatment, and CGA prevented increases in TLR2, TLR9 and Myd88 following HSV-1 challenge in BV2 cells both at the mRNA and protein levels. Moreover, CGA could attenuate HSV-induced TNF-α and IL-6 release into the supernatant. The mRNA levels of TNF-α and IL-6 were also significantly inhibited by CGA. The expression of NF-κB p65 increased significantly in the nucleus in HSV-1-stimulated microglia but could be reduced by CGA.


CONCLUSIONS
CGA inhibits the inflammatory reaction in HSE via the suppression of TLR2/TLR9-Myd88 signaling pathways. CGA may serve as an anti-inflammatory agent and provide a new strategy for treating HSE.
Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, PR China.
Yuan-Jin
YJ
Guo
Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, PR China; Department of Neurology, Wuhan Central Hospital, Wuhan 430014, PR China.
Tao
T
Luo
Department of Neurology, Wuhan General Hospital of Guangzhou Military Command, Wuhan 430070, PR China.
Fei
F
Wu
Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, PR China.
Yuan-Wu
YW
Mei
Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, PR China.
Jun
J
Peng
Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, PR China.
Huan
H
Liu
Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, PR China.
Hua-Rong
HR
Li
Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, PR China.
Shu-Ling
SL
Zhang
Central Lab, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, PR China.
Ji-Hua
JH
Dong
Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, PR China.
Yuan
Y
Fang
Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, PR China. Electronic address: leizhao@hust.edu.cn.
Lei
L
Zhao
D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002726:Chlorogenic Acid / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism; D006561:Herpes Simplex / Q000473:pathology* / Q000821:virology; D018259:Herpesvirus 1, Human; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D017628:Microglia / Q000187:drug effects*; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051195:Toll-Like Receptor 2 / Q000096:biosynthesis / Q000187:drug effects*; D051217:Toll-Like Receptor 9 / Q000096:biosynthesis / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D015850:Interleukin-6; D016328:NF-kappa B; D051195:Toll-Like Receptor 2; D051217:Toll-Like Receptor 9; D014409:Tumor Necrosis Factor-alpha; D002726:Chlorogenic Acid
Chlorogenic acid; Herpes simplex virus-1; Inflammation; Toll-like receptor 2; Toll-like receptor 9