Lysophosphatidic acid stimulates inflammatory cascade in airway epithelial cells.
Nasal polyps are benign outgrowths originating from the anterior ethmoid and maxillary sinuses. The events leading to polyp formation are unknown but evidence points to damage of the mucousal epithelium. Lysophosphatidic acid (LPA) is a water-soluble phospholipid that has been implicated in the development of allergic inflammation. We hypothesized LPA may be an important mediator in the initiation and maintenance of the inflammatory milieu of the polyp. Data was compared from unstimulated lung epithelial and when possible nasal polyp-derived epithelial cells with LPA stimulated cells. LPA receptors 1 and 2 were constitutively expressed on lung and nasal polyp-derived epithelial cells and receptor mRNA expression was decreased upon stimulation with IL-13 and IFN-gamma. When cells were treated with LPA, cellular proliferation was stimulated 2.2 fold. Supernatants from LPA stimulated cells displayed decreases in the levels of VEGF, GM-CSF, and TNF-alpha at 24h which returned to normal or increased at 48h. Our results suggest epithelial cells undergo rapid proliferation in response to LPA resulting in a transient decrease in inflammatory cytokines followed by an upregulation of these cytokines that could lead to increased inflammation.
Barekzi
Elizabeth
E
Asthma and Allergic Disease Center, Beirne Carter Center for Immunology, Department of Medicine, University of Virginia Health System, Charlottesville, VA, USA.
Roman
Jessica
J
Hise
Kathleen
K
Georas
Steve
S
Steinke
John W
JW
D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000139:chemically induced*; D008168:Lung / Q000187:drug effects* / Q000276:immunology; D008246:Lysophospholipids / Q000494:pharmacology*; D009297:Nasal Mucosa / Q000187:drug effects* / Q000276:immunology; D009298:Nasal Polyps / Q000276:immunology*; D049368:Receptors, Lysophosphatidic Acid / Q000378:metabolism
D018925:Chemokines; D016207:Cytokines; D008246:Lysophospholipids; D049368:Receptors, Lysophosphatidic Acid; C032881:lysophosphatidic acid