Immunosuppressant triptolide inhibits dendritic cell-mediated chemoattraction of neutrophils and T cells through inhibiting Stat3 phosphorylation and NF-kappaB activation.
Triptolide, an active component purified from the medicinal plant Tripterygium wilfordii Hook F., is potent in anti-inflammation and immunosuppression. Dendritic cells (DC), one of important targets of immunosuppressants, play crucial roles in linking the innate immunity and adaptive immunity. However, the effects of triptolide on DC have not been fully elucidated. Chemoattraction of neutrophils and T cells by DC may favor their interactions and initiation of immune response. Here we demonstrate that triptolide significantly impairs DC-mediated chemoattraction of neutrophils and T cells both in vitro and in vivo by suppressing DC production of CC and CXC chemokines including MIP-1alpha, MIP-1beta, MCP-1, RANTES, TARC, and IP-10 in response to LPS. Furthermore, triptolide-mediated inhibition of NF-kappaB activation, Stat3 phosphorylation and increase of SOCS1 expression in DC may be involved in the inhibitory effect of triptolide. Our study provides a novel mechanistic explanation for the anti-inflammatory and immunosuppressive activities of triptolide.
Liu
Qiuyan
Q
Institute of Immunology, Zhejiang University, Hangzhou 310031, PR China.
Chen
Taoyong
T
Chen
Guoyou
G
Li
Nan
N
Wang
Jianli
J
Ma
Pengcheng
P
Cao
Xuetao
X
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000166:cytology; D003713:Dendritic Cells / Q000166:cytology* / Q000378:metabolism; D004224:Diterpenes / Q000494:pharmacology*; D004852:Epoxy Compounds; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism*; D009504:Neutrophils / Q000166:cytology*; D010616:Phenanthrenes / Q000494:pharmacology*; D010766:Phosphorylation; D012097:Repressor Proteins / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D004224:Diterpenes; D004852:Epoxy Compounds; D007166:Immunosuppressive Agents; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; D010616:Phenanthrenes; D012097:Repressor Proteins; C108944:SOCS1 protein, human; D050796:STAT3 Transcription Factor; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; C001899:triptolide