Dual role of shikonin in early and late stages of collagen type II arthritis.
OBJECTIVE
To investigate the anti-inflammatory or immunomodulatory effect of shikonin on early stage and established murine collagen-induced arthritis (CIA).


METHODS
Mouse were injected intraperitoneally with shikonin (5 mg/kg) for 10 days along before or after the onset of CIA. The arthritis response was monitored visually by macroscopic scoring. Reverse transcription-polymerase chain reaction and western blotting were employed to determine the mRNA and protein expression of cytokine in patella with adjacent synovium in CIA mouse. Histology of knee was used to assess the occurrence of cartilage destruction and bone erosion.


RESULTS
Shikonin (5 mg/kg) treatment along had no effect on macroscopic score and incidence of arthritis on early stage of CIA. However, a pronounced amelioration of macroscopic score and cartilage destruction was found in mouse treated with shikonin on established CIA for 10 days. Moreover, The mRNA levels of Th1 cytokines [tumor necrosis factor-alpha and interleukin (IL)-12] was significantly inhibited both in the synovial tissue and in the articular cartilage in treated groups compared with those in control groups, whereas the mRNA and protein levels of Th2 cytokines (IL-10 and IL-4) remained elevated throughout the treatment period. Moreover, the inflammatory cytokine, the mRNA and protein levels of IL-6 was down-regulated in mice with established CIA after treatment with shikonin. T-box expressed in T cells (T-bet) mRNA levels were decreased in shikonin compared with control group, and GATA-3 mRNA levels were higher than that in control group.


CONCLUSIONS
Shikonin treatment on established CIA can inhibit Th1 cytokines expression and induce Th2 cytokines expression in mice with established CIA. The inhibited effect of shikonin on Th1 cytokines expression may be mediated not only by inhibiting Th1 responses through T-bet mechanism, but also by inducing anti-inflammatory mediators such as IL-10 and IL-4 through a GATA-3 dependent mechanism.
Dai
Qiaomei
Q
Department of Rheumatology, The Second Affiliated Hospital, Harbin Medical University, Bao Jian Road, Harbin, 150086, People's Republic of China.
Fang
Jianghong
J
Zhang
Feng-shan
FS
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000473:pathology; D002358:Cartilage, Articular / Q000473:pathology; D024043:Collagen Type II / Q000009:adverse effects; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D050990:GATA3 Transcription Factor / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000276:immunology; D007378:Interleukins / Q000032:analysis; D007719:Knee Joint / Q000473:pathology; D051379:Mice; D009285:Naphthoquinones / Q000008:administration & dosage / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D013583:Synovial Membrane / Q000473:pathology; D016896:Treatment Outcome
D000894:Anti-Inflammatory Agents, Non-Steroidal; D024043:Collagen Type II; D016207:Cytokines; D050990:GATA3 Transcription Factor; D007378:Interleukins; D009285:Naphthoquinones; D012333:RNA, Messenger; C016101:shikonin
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