PMID- 30905278
OWN - NLM
STAT- MEDLINE
DCOM- 20190418
LR  - 20200225
IS  - 1744-5116 (Electronic)
IS  - 1388-0209 (Print)
IS  - 1388-0209 (Linking)
VI  - 57
IP  - 1
DP  - 2019 Dec
TI  - beta-Sitosterol modulates macrophage polarization and attenuates rheumatoid 
      inflammation in mice.
PG  - 161-168
LID - 10.1080/13880209.2019.1577461 [doi]
AB  - CONTEXT: beta-Sitosterol (BS), the primary constituent of plants and vegetables, 
      exhibits multiple biological effects. OBJECTIVE: This study explores its effect 
      of immune-regulation on macrophages and its potential for rheumatoid arthritis 
      (RA) therapy. MATERIALS AND METHODS: In vitro, bone marrow-derived macrophages 
      (BMDMs) were treated with 5, 25 and 50 muM BS in the M1 or M2 polarization 
      conditions. In vivo, either i.p. injection with 20 or 50 mg/kg BS every 2 d after 
      boost immunization of collagen-induced arthritis (CIA) or adoptive transfer of 
      2 x 10(6) BS-treated BMDMs (BS-BMDMs) at the day before CIA were adopted in mice 
      to test the therapeutic effect. IL-10 antibody depletion was used in the period 
      of above treatments to discuss the underlying mechanism. RESULTS: The phenotypes 
      and function of BMDMs showed that 5, 25 and 50 muM BS significantly repressed the 
      M1 polarization and augmented M2 polarization dependent upon concentration. The 
      expression of iNOS, IL-1beta, CD86 and MHCII in 25 muM BS-treated M1-polarized BMDMs 
      was reduced by 50.2, 47.1, 87.1 and 31.3%, respectively. In contrast, the 
      expression of arginase-1, IL-10, CD163 and CD206 in 25 muM BS-treated M2-polarized 
      BMDMs was increased by 65.6, 107.4, 23.5 and 51.3%, respectively. In CIA mice, 
      either i.p. injection with BS or adoptive transfer of BS-BMDMs could alleviate 
      the symptoms of ankle swelling (vehicle group: 3.13 +/- 0.102 mm; 20 mg/kg BS 
      group: 2.64 +/- 0.043 mm; 50 mg/kg BS group: 2.36 +/- 0.084 mm; BMDMs group: 
      3.09 +/- 0.174 mm; BS-BMDMs group: 2.43 +/- 0.042 mm), reduce the levels of 
      collagen-specific antibodies (IgG and IgG1, but not IgG2c, p < 0.05) and inhibit 
      the production of pro-inflammatory cytokines (p < 0.05). Depletion of IL-10 
      counteracted the effect of BS treatment (alpha-IL-10 vs. RatIgG1, p < 0.01 on day 
      16), highlighting the role of IL-10 in the anti-inflammatory response. 
      CONCLUSIONS: These results suggested that BS could modulate the functions of 
      macrophages and might be a promising agent for RA therapy.
FAU - Liu, Rui
AU  - Liu R
AD  - a Department of Rheumatism , Suzhou Hospital Affiliated to Nanjing University of 
      Chinese Medicine , Suzhou , PR China.
FAU - Hao, Donglin
AU  - Hao D
AD  - a Department of Rheumatism , Suzhou Hospital Affiliated to Nanjing University of 
      Chinese Medicine , Suzhou , PR China.
FAU - Xu, Wenya
AU  - Xu W
AD  - a Department of Rheumatism , Suzhou Hospital Affiliated to Nanjing University of 
      Chinese Medicine , Suzhou , PR China.
FAU - Li, Jinjin
AU  - Li J
AD  - a Department of Rheumatism , Suzhou Hospital Affiliated to Nanjing University of 
      Chinese Medicine , Suzhou , PR China.
FAU - Li, Xiaoru
AU  - Li X
AD  - a Department of Rheumatism , Suzhou Hospital Affiliated to Nanjing University of 
      Chinese Medicine , Suzhou , PR China.
FAU - Shen, Dong
AU  - Shen D
AD  - a Department of Rheumatism , Suzhou Hospital Affiliated to Nanjing University of 
      Chinese Medicine , Suzhou , PR China.
AD  - b Department of Rheumatism , Suzhou Science & Technology Town Hospital , Suzhou , 
      PR China.
FAU - Sheng, Kang
AU  - Sheng K
AD  - a Department of Rheumatism , Suzhou Hospital Affiliated to Nanjing University of 
      Chinese Medicine , Suzhou , PR China.
FAU - Zhao, Lin
AU  - Zhao L
AD  - a Department of Rheumatism , Suzhou Hospital Affiliated to Nanjing University of 
      Chinese Medicine , Suzhou , PR China.
FAU - Xu, Weiwei
AU  - Xu W
AD  - a Department of Rheumatism , Suzhou Hospital Affiliated to Nanjing University of 
      Chinese Medicine , Suzhou , PR China.
FAU - Gao, Zhongen
AU  - Gao Z
AD  - a Department of Rheumatism , Suzhou Hospital Affiliated to Nanjing University of 
      Chinese Medicine , Suzhou , PR China.
FAU - Zhao, Xu
AU  - Zhao X
AD  - a Department of Rheumatism , Suzhou Hospital Affiliated to Nanjing University of 
      Chinese Medicine , Suzhou , PR China.
FAU - Liu, Qiuhong
AU  - Liu Q
AD  - a Department of Rheumatism , Suzhou Hospital Affiliated to Nanjing University of 
      Chinese Medicine , Suzhou , PR China.
FAU - Zhang, Yiting
AU  - Zhang Y
AD  - a Department of Rheumatism , Suzhou Hospital Affiliated to Nanjing University of 
      Chinese Medicine , Suzhou , PR China.
LA  - eng
PT  - Journal Article
PL  - England
TA  - Pharm Biol
JT  - Pharmaceutical biology
JID - 9812552
RN  - 0 (Cytokines)
RN  - 0 (Sitosterols)
RN  - 130068-27-8 (Interleukin-10)
RN  - 5LI01C78DD (gamma-sitosterol)
SB  - IM
MH  - Animals
MH  - Arthritis, Experimental/*drug therapy/immunology
MH  - Bone Marrow Cells/*drug effects/*immunology
MH  - Cell Polarity/drug effects/immunology
MH  - Cytokines/biosynthesis/blood/immunology
MH  - Dose-Response Relationship, Drug
MH  - Interleukin-10/biosynthesis/immunology
MH  - Macrophage Activation/drug effects
MH  - Macrophages/*drug effects/*immunology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Sitosterols/*pharmacology
PMC - PMC6442231
OTO - NOTNLM
OT  - M2 macrophages
OT  - Rheumatoid arthritis
OT  - collagen-induced arthritis
EDAT- 2019/03/25 06:00
MHDA- 2019/04/19 06:00
PMCR- 2019/03/24
CRDT- 2019/03/26 06:00
PHST- 2019/03/26 06:00 [entrez]
PHST- 2019/03/25 06:00 [pubmed]
PHST- 2019/04/19 06:00 [medline]
PHST- 2019/03/24 00:00 [pmc-release]
AID - 1577461 [pii]
AID - 10.1080/13880209.2019.1577461 [doi]
PST - ppublish
SO  - Pharm Biol. 2019 Dec;57(1):161-168. doi: 10.1080/13880209.2019.1577461.