title: Transforming growth factor-β1 modulates lipopolysaccharide-induced cytokine/chemokine production and inhibits nuclear factor-κB, extracellular signal-regulated kinases and p38 activation in dendritic cells in mice.
abstract: Tolerogenic dendritic cells (DCs) are crucial for peripheral tolerance mediated by a variety of cytokines, including transforming growth factor-β1 (TGF-β1). We have observed that TGF-β1-treated DCs (TGFβ-DCs) were resistant to the maturation stimulus of lipopolysaccharide (LPS) and that TGF-β1 down-regulated Toll-like receptor 4 (TLR4) expression on DCs. The purpose of this study was to analyze whether TGF-β1 affected the production of cytokines/chemokines and proteins in the TLR4 signal transduction pathway following LPS stimulation. We observed that TGF-β1 induced a significant increase in interleukin (IL)-10, impaired IL-12 secretion, and attenuated messenger RNA (mRNA) expression of chemokines CCL2, CCL3, and CXCL10 in DCs following LPS administration. We also noted that TGF-β1 suppressed LPS-induced activation of nuclear factor (NF)-κB, extracellular signal-related kinases (ERK)-1/2, and p38 in DCs. Taken together, our results identified the suppressive effects of TGF-β1 on TLR4 signal transduction, strengthening the notion that TGFβ-DCs are a unique type of tolerogenic DC exhibiting distinct characteristics.
authors.affiliation: Department of Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, People's Republic of China. mouhaibo@zju.edu.cn
authors.forename: H B
authors.initials: HB
authors.lastname: Mou
authors.forename: M F
authors.initials: MF
authors.lastname: Lin
authors.forename: H
authors.initials: H
authors.lastname: Huang
authors.forename: Z
authors.initials: Z
authors.lastname: Cai
mesh_terms: D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D018925:Chemokines / Q000096:biosynthesis*; D016207:Cytokines / Q000096:biosynthesis*; D017931:DNA Primers; D003713:Dendritic Cells / Q000187:drug effects* / Q000201:enzymology; D024202:Electrophoretic Mobility Shift Assay; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053773:Transforming Growth Factor beta1 / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D018925:Chemokines; D016207:Cytokines; D017931:DNA Primers; D008070:Lipopolysaccharides; D016328:NF-kappa B; D053773:Transforming Growth Factor beta1; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases