PMID- 18850043
OWN - NLM
STAT- MEDLINE
DCOM- 20081216
LR  - 20131121
IS  - 0379-0355 (Print)
IS  - 0379-0355 (Linking)
VI  - 30
IP  - 6
DP  - 2008 Jul-Aug
TI  - Prevention of type 1 diabetes by immature dendritic cells treated with an ethanol 
      extract of Paecilomyces hepiali Chen mycelium.
PG  - 421-9
LID - 10.1358/mf.2008.30.6.1186083 [doi]
AB  - Dendritic cells (DCs) classically promote immune responses but can be manipulated 
      to induce antigen-specific hyporesponsiveness. It has been shown that 
      phenotypically "immature" DCs, defined by low levels of costimulatory molecules 
      at the cell surface, are involved in the induction of peripheral immune tolerance 
      in autoimmunity. Paecilomyces hepiali Chen (PHC) mycelium, as a substitute for 
      Cordyceps, has been used extensively as an immunomodulator to treat numerous 
      diseases. In this study, the effects of an ethanol extract of PHC (EEPHC) on the 
      phenotypic and functional maturation of bone marrow-derived DCs (BM-DCs) from NOD 
      mice were evaluated. EEPHC significantly suppressed the expression of major 
      histocompatibility complex (MHC) class II molecules and the costimulatory 
      molecules CD40 and CD86 in NOD BM-DCs. These DCs also exhibited impaired 
      production of the proinflammatory cytokine interleukin-12 (IL-12) and poor 
      stimulatory capacity in the presence of EEPHC. Moreover, inhibition of the 
      activation and differentiation of cultured DCs was associated with reduced DNA 
      binding activity of nuclear factor kappa B (NF- kappaB), a transcription factor 
      recently shown to be responsible for DC maturation. Administration of 3x10(5) 
      EEPHC-treated DCs into NOD mice aged 3-4 weeks effectively prevented the onset of 
      diabetes. Furthermore, splenocytes from the protected mice produced high amounts 
      of IL-4 and IL-10 and low levels of IL-2 and interferon gamma, suggesting that 
      these DCs deficient in NF- kappaB activity are responsible for the apparent shift 
      in type 2 helper T cells. These novel results showed that EEPHC could 
      specifically inhibit NF- kappaB activity and maintain DCs in a potentially 
      tolerogenic state, permitting their use in strategies to induce immune tolerance 
      in type 1 diabetes.
CI  - Copyright 2008 Prous Science, S.A.U. or its licensors. All rights reserved.
FAU - Zhang, Chengliang
AU  - Zhang C
AD  - Department of Pharmacology, Tongji Pharmaceutical College, HuaZhong University of 
      Science and Technology, Wuhan, China. xiangming517@yahoo.com
FAU - Zou, Xiaolei
AU  - Zou X
FAU - Leluo, Guan
AU  - Leluo G
FAU - Xu, Jing
AU  - Xu J
FAU - Xiang, Ming
AU  - Xiang M
LA  - eng
PT  - Journal Article
PL  - Spain
TA  - Methods Find Exp Clin Pharmacol
JT  - Methods and findings in experimental and clinical pharmacology
JID - 7909595
RN  - 0 (Cytokines)
RN  - 0 (Indicators and Reagents)
RN  - 0 (NF-kappa B)
RN  - 0 (Solvents)
RN  - 3K9958V90M (Ethanol)
SB  - IM
MH  - Animals
MH  - Bone Marrow Cells/drug effects
MH  - Cell Transplantation
MH  - Cytokines/biosynthesis
MH  - Dendritic Cells/*drug effects/*transplantation
MH  - Diabetes Mellitus, Type 1/pathology/*prevention & control
MH  - Electrophoretic Mobility Shift Assay
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Ethanol
MH  - Female
MH  - Flow Cytometry
MH  - Genes, MHC Class II/genetics
MH  - Indicators and Reagents
MH  - Mice
MH  - Mice, Inbred NOD
MH  - Mycelium/*chemistry
MH  - NF-kappa B/metabolism
MH  - Paecilomyces/*chemistry
MH  - Phenotype
MH  - Solvents
MH  - T-Lymphocytes, Helper-Inducer/physiology
EDAT- 2008/10/14 09:00
MHDA- 2008/12/17 09:00
CRDT- 2008/10/14 09:00
PHST- 2008/10/14 09:00 [pubmed]
PHST- 2008/12/17 09:00 [medline]
PHST- 2008/10/14 09:00 [entrez]
AID - 1186083 [pii]
AID - 10.1358/mf.2008.30.6.1186083 [doi]
PST - ppublish
SO  - Methods Find Exp Clin Pharmacol. 2008 Jul-Aug;30(6):421-9. doi: 
      10.1358/mf.2008.30.6.1186083.