TGF-β1 treated murine dendritic cells are maturation resistant and down-regulate Toll-like receptor 4 expression

Objective: To explore the effects of transforming growth factor (51 (TGF-β1) on dendritic cells (DC). Methods: Murine bone marrow cells were cultured with GM-CSF and TGF-β1 to develop TGF-β1-treated DC (TGFβ-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 TGFβ-DC express lower CD80, CD86,I-Ab and CD40. The TGFβ-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-β1 could down-regulate TLR4 expression on TGFβ-DC. Conclusion: TGFβ-DC are resistant to maturation stimulus (LPS) and might have some correlation with the down-modulation of TLR4 expression.

Objective: To explore the effects of transforming growth factor β1(TGF-β1) on dendritic cells (DC). Methods: Murine bone marrow cells were cultured with GM-CSF and TGF-β1 to develop TGF-β1-treated DC (TGFβ-DC). Then they were stimulated by lipopolysaccharide (LPS). Their phenotypes were assessed by flow cytometry (FCM). The allogeneicstimulating 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 TGFβ-DC express lower CD80, CD86, I-A^b and CD40. The TGFβ-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-β1 could down-regulate TLR4 expression on TGFβ-DC. Conclusion: TGFβ-DC are resistant to maturation stimulus (LPS) and might have some correlation with the down-modulation of TLR4 expression.