Title: Diesel exhaust particle-treated human bronchial epithelial cells upregulate Jagged-1 and OX40 ligand in myeloid dendritic cells via thymic stromal lymphopoietin.
Authors: Bleck, Bertram; Tse, Doris B; Gordon, Terry; Ahsan, Mohammad R; Reibman, Joan
Published In J Immunol, (2010 Dec 01)
Abstract: Ambient particulate matter, including diesel exhaust particles (DEP), promotes the development of allergic disorders. DEP increase oxidative stress and influence human bronchial epithelial cell (HBEC)-dendritic cell interactions via cytokines, including thymic stromal lymphopoietin (TSLP). Upregulation of TSLP results in Th2 responses. Using primary culture HBEC and human myeloid dendritic cell (mDC) cocultures, we show in this study that DEP upregulation of Th2 responses occurred via HBEC-dependent mechanisms that resulted from oxidative stress. Moreover, DEP-treated HBEC and ambient particulate matter-treated HBEC upregulated OX40 ligand (OX40L) and the Notch ligand Jagged-1 mRNA and expression on mDC. Upregulation of OX40L as well as Jagged-1 on mDC required HBEC and did not occur in the presence of N-acetylcysteine. Furthermore, OX40L and Jagged-1 upregulation was inhibited when HBEC expression of TSLP was silenced. Thus, DEP treatment of HBEC targeted two distinct pathways in mDC that were downstream of TSLP expression. Upregulation of OX40L and Jagged-1 by mDC resulted in mDC-driven Th2 responses. These studies expand our understanding of the mechanism by which ambient pollutants alter mucosal immunity and promote disorders such as asthma.
PubMed ID: 20974985
MeSH Terms: Bronchi/cytology; Bronchi/drug effects; Bronchi/immunology; Calcium-Binding Proteins/biosynthesis*; Cell Polarity/drug effects; Cell Polarity/immunology; Cells, Cultured; Coculture Techniques; Cytokines/physiology*; Dendritic Cells/drug effects; Dendritic Cells/immunology*; Dendritic Cells/metabolism; Humans; Intercellular Signaling Peptides and Proteins/biosynthesis*; Jagged-1 Protein; Membrane Proteins/biosynthesis*; Myeloid Cells/drug effects; Myeloid Cells/immunology; Myeloid Cells/metabolism; OX40 Ligand/biosynthesis*; Particulate Matter/toxicity*; Reactive Oxygen Species/toxicity; Receptors, Notch/biosynthesis; Respiratory Mucosa/cytology; Respiratory Mucosa/drug effects; Respiratory Mucosa/immunology*; Serrate-Jagged Proteins; Signal Transduction/drug effects; Signal Transduction/immunology; Stromal Cells/drug effects; Stromal Cells/immunology; Stromal Cells/metabolism; Th2 Cells/drug effects; Th2 Cells/immunology; Th2 Cells/metabolism; Thymus Gland/cytology; Thymus Gland/drug effects; Thymus Gland/immunology; Up-Regulation/drug effects; Up-Regulation/immunology*; Vehicle Emissions/toxicity*