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

• Published in: Transplantation proceedings Vol. 43; no. 5; pp. 2049 - 2052
• Main Authors: Mou, H.B, Lin, M.F, Huang, H, Cai, Z
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01-06-2011; Elsevier
• Subjects: Animals; Base Sequence; Biological and medical sciences; Blotting, Western; Chemokines - biosynthesis; Cytokines - biosynthesis; Dendritic Cells - drug effects; Dendritic Cells - enzymology; DNA Primers; Electrophoretic Mobility Shift Assay; Enzyme Activation; Extracellular Signal-Regulated MAP Kinases - metabolism; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Lipopolysaccharides - pharmacology; Medical sciences; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; NF-kappa B - antagonists & inhibitors; p38 Mitogen-Activated Protein Kinases - metabolism; Reverse Transcriptase Polymerase Chain Reaction; Surgery; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Tissue, organ and graft immunology; Transforming Growth Factor beta1 - physiology; Dendritic cell; Extracellular signal-regulated protein kinase; Enzyme; Transferases; Rodentia; Cytokine; Mitogen-activated protein kinase; Accessory cell; Activation; Biosynthesis; Chemokine; Vertebrata; Mammalia; Treatment; Mouse; Antigen presenting cell; Surgery; Animal; Production; Lipopolysaccharide; Graft; Inhibitor; Transforming growth factor β1; Transcription factor NFκB
• ISSN: 0041-1345; 1873-2623
• DOI: 10.1016/j.transproceed.2011.02.054

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.