TGF-beta1 treated murine dendritic cells are maturation resistant and down-regulate Toll-like receptor 4 expression.
OBJECTIVE
To explore the effects of transforming growth factor beta1 (TGF-beta1) on dendritic cells (DC).


METHODS
Murine bone marrow cells were cultured with GM-CSF and TGF-beta1 to develop TGF-beta1-treated DC (TGFbeta-DC). Then they were stimulated by lipopolysaccharide (LPS). Their phenotypes were assessed by flow cytometry (FCM). The allogeneic stimulating capacity of DC was measured by mixed lymphocyte reaction (MLR) using BrdU ELISA method and IL-12p70 protein was detected by ELISA. The expression of Toll-like receptor 4 (TLR4) was analyzed by semi quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and FCM.


RESULTS
Compared to immature DC (imDC) cultured by GM-CSF alone, the TGFbeta-DC express lower CD80, CD86, I-Ab and CD40. The TGFbeta-DC were resistant to maturation with LPS. Maturation resistance was evident from a failure to up-regulate co-stimulatory molecules (CMs), to stimulate larger T cells proliferation and to enhance secretion of IL-12p70. We also found that TGF-beta1 could down-regulate TLR4 expression on TGFbeta-DC.


CONCLUSIONS
TGFbeta-DC are resistant to maturation stimulus (LPS) and might have some correlation with the down-modulation of TLR4 expression.
Mou
Hai-bo
HB
Department of Bone Marrow Transplantation Center, First Affiliated Hospital, Medical College, Zhejiang University, Hangzhou 310003, China. mouzxr@hzcnc.com
Lin
Mao-fang
MF
Cen
Hong
H
Yu
Jing
J
Meng
Xiao-jian
XJ
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology / Q000378:metabolism*; D003713:Dendritic Cells / Q000187:drug effects* / Q000502:physiology*; D015536:Down-Regulation / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011956:Receptors, Cell Surface / Q000276:immunology / Q000378:metabolism*; D051197:Toll-Like Receptor 4; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1
D016207:Cytokines; D008070:Lipopolysaccharides; D011956:Receptors, Cell Surface; C508961:Tgfb1 protein, mouse; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1