Abstract:
:Airway neutrophilia is a prominent feature of chronic obstructive pulmonary disease. As cigarette smoke (CS) and epidermal growth factor (EGF) both cause release of interleukin-8 (IL-8) from epithelial cells in vitro, we investigated whether autocrine ligands for the EGF receptor (EGFR) are involved in this proinflammatory response to CS. NCI-H292 or primary bronchial epithelial cells were cultured with or without cigarette smoke extract (CSE) or EGF for 6-48 h. We then tested culture supernatants for lactate dehydrogenase activity to assess cell viability, and for IL-8 and EGFR ligands by ELISA; quantitative RT-PCR was used to measure IL-8 and EGFR ligand mRNA. EGF and low concentrations of CSE both promoted cell survival and caused enhanced transcription and release of IL-8. Similarly, levels of mRNA encoding transforming growth factor alpha (TGF-alpha), heparin-binding EGF-like growth factor, and amphiregulin (AR) were increased, as was shedding of TGF-alpha and AR protein into the culture medium. With the exception of AR gene transcription, the CS-induced responses were blocked by the EGFR-selective kinase inhibitor AG1478. Furthermore, ~ 45% of CS-induced IL-8 release was inhibited by a neutralising anti-EGFR. Our data indicate that secretion of IL-8 in response to CSE is dependent on EGFR activation and that autocrine production of TGF-alpha makes a substantial contribution to this response.
journal_name
Am J Respir Cell Mol Biolauthors
Richter A,O'Donnell RA,Powell RM,Sanders MW,Holgate ST,Djukanović R,Davies DEdoi
10.1165/ajrcmb.27.1.4789keywords:
subject
Has Abstractpub_date
2002-07-01 00:00:00pages
85-90issue
1eissn
1044-1549issn
1535-4989journal_volume
27pub_type
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journal_title:American journal of respiratory cell and molecular biology
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journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
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journal_title:American journal of respiratory cell and molecular biology
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