Paeoniflorin inhibits TGF-beta1-mediated collagen production by Schistosoma japonicum soluble egg antigen in vitro.
The main pathological characteristics of hepatic fibrosis in schistosomiasis are the proliferation of hepatic stellate cells (HSCs) and the deposition of collagen type I (Col I) and collagen type III (Col III). Transforming growth factor beta-1 (TGF-beta1) plays an important role in hepatic fibrosis. Paeoniflorin (PAE) has been reported to have immunoregulatory effects; however, the mechanism of its anti-hepatic fibrosis in S. japonicum has not been elucidated. In the present study, we found that mouse peritoneal macrophages (PMphis) stimulated by soluble egg antigen (SEA) of S. japonicum could secrete TGF-beta1, and the TGF-beta1 in the peritoneal macrophage-conditioned medium (PMCM) could induce proliferation of HSCs and secretion of Col I and III. We selected PMCM at 1 : 2 dilution as the optimum PMCM (OPMCM). Then we treated HSCs pre-incubated with OPMCM with PAE, and found that the inhibition of HSC proliferation or Col I and III production were closely correlated with the concentration of PAE. Further investigation found that PAE significantly decreased the Smad3 transcription and phosphorylation in HSCs stimulated by OPMCM. In conclusion, SEA plays a key role in hepatic fibrosis by inducing TGF-beta1 from PMphis. PAE can exert anti-fibrogenic effects by inhibiting HSCs proliferation and down-regulating Smad3 expression and phosphorylation through TGF-beta1 signalling.
Chu
D
D
Institute of Clinical Pharmacology, Anhui Medical University and the Key Laboratory of Antiinflammatory-immunopharmacology, Anhui, China.
Luo
Q
Q
Li
C
C
Gao
Y
Y
Yu
L
L
Wei
W
W
Wu
Q
Q
Shen
J
J
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000947:Antigens, Helminth / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D001952:Bridged-Ring Compounds / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000235:genetics / Q000378:metabolism*; D017077:Culture Media, Conditioned / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D005960:Glucosides / Q000494:pharmacology*; D022781:Hepatocytes / Q000187:drug effects; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D039821:Monoterpenes; D010063:Ovum / Q000737:chemistry; D010766:Phosphorylation / Q000187:drug effects; D012549:Schistosoma japonicum / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D051785:Smad Proteins / Q000037:antagonists & inhibitors / Q000235:genetics; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D006027:Glycosides
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000947:Antigens, Helminth; D001565:Benzoates; D001952:Bridged-Ring Compounds; D003094:Collagen; D017077:Culture Media, Conditioned; D005960:Glucosides; D039821:Monoterpenes; D051785:Smad Proteins; D053773:Transforming Growth Factor beta1; C015423:peoniflorin; D006027:Glycosides