Format

Send to

Choose Destination
J Interferon Cytokine Res. 2009 May;29(5):273-84. doi: 10.1089/jir.2008.0076.

IL-1beta augments TNF-alpha-mediated inflammatory responses from lung epithelial cells.

Author information

1
Department of Environmental Medicine, University of Rochester School of Medicine, Rochester, New York 14642, USA. Sara_Saperstein@urmc.rochester.edu

Abstract

Interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) mediate the development of numerous inflammatory lung diseases. Since IL-1beta is typically activated in situations where TNF-alpha is produced, it was hypothesized that IL-1beta alters TNF-alpha-induced proinflammatory epithelial cell function by altering TNF receptor shedding and surface abundance. In this study, the impact of IL-1beta on TNF-alpha-mediated chemokine production as well as TNF receptor surface expression and shedding were investigated from mouse pulmonary epithelial cells (MLE-15). Interleukin-1beta rapidly and persistently enhanced soluble and surface TNFR2. These effects were dependent on TNFR1 expression. TNFR2 small-interfering RNA (siRNA) shifted IL-1beta responses, significantly increasing surface and shed TNFR1 implying IL-1beta selectively modifies TNF receptors depending on cellular receptor composition. mRNA expression of both receptors was unaltered by IL-1beta up to 24 h or in combination with TNF-alpha indicating effects were post-transcriptional. Interleukin-1beta pretreatment enhanced TNF-alpha-induced macrophage inflammatory protein (MIP)-2 and KC mRNA expression as well as MIP-2 and KC protein levels at the same time point analyzed. Experiments utilizing siRNA against the TNF receptors and a TNFR1 neutralizing antibody demonstrated TNF-alpha induced MIP-2 through TNFR1, whereas both receptors may have contributed to KC production. These data suggest IL-1beta modulates TNF-alpha-mediated inflammatory lung diseases by enhancing epithelial cell TNF receptor surface expression.

PMID:
19231998
PMCID:
PMC2718541
DOI:
10.1089/jir.2008.0076
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Atypon Icon for PubMed Central
Loading ...
Support Center