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.