Apolipoprotein E Signals via TLR4 to Induce CXCL5 Secretion by Asthmatic Airway Epithelial Cells.

Apolipoprotein E Signals via TLR4 to Induce CXCL5 Secretion by Asthmatic Airway Epithelial Cells. Am J Respir Cell Mol Biol. 2020 Apr 27;: Authors: Kalchiem-Dekel O, Yao X, Barochia AV, Kaler M, Figueroa DM, Karkowsky WB, Gordon EM, Gao M, Fergusson MM, Qu X, Liu P, Li Y, Seifuddin F, Pirooznia M, Levine SJ Abstract The primary function of apolipoprotein E (APOE) is to mediate the transport of cholesterol- and lipid-containing lipoprotein particles into cells by receptor-mediated endocytosis. APOE also has pro- and anti-inflammatory effects, which are both context- and concentration-dependent. For example, Apoe-/- mice have enhanced airway remodeling and hyperreactivity in experimental asthma, whereas increased APOE levels in lung epithelial lining fluid induce IL-1β secretion from human asthmatic alveolar macrophages. However, APOE-mediated airway epithelial cell inflammatory responses and signaling pathways have not been defined. Here, RNA-sequencing of human asthmatic bronchial brushing cells stimulated with APOE identified the increased expression of mRNA transcripts encoding multiple pro-inflammatory genes, including CXCL5 (C-X-C Motif Chemokine Ligand 5), an epithelial-derived chemokine that promotes neutrophil activation and chemotaxis. We subsequently characterized the APOE signaling pathway that induces CXCL5 secretion by human asthmatic small airway epithelial cells (SAECs). Neutralizing antibodies directed against TLR4, b...
Source: American Journal of Respiratory Cell and Molecular Biology - Category: Molecular Biology Authors: Tags: Am J Respir Cell Mol Biol Source Type: research