Current Respiratory Medicine Reviews

Joseph Varon  
The University of Texas Health Science Center
Houston, TX
USA

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Interleukin-1, Neutrophil Elastase, and Lipopolysaccharide: Key Pro- Inflammatory Stimuli Regulating Inflammation in Cystic Fibrosis

Author(s): Tomas P. Carroll, Catherine M. Greene, Clifford C. Taggart, Noel G. McElvaney, Shane J. O'Neill.

Abstract:

Cystic fibrosis (CF) is a common fatal genetic disease among Caucasians of European descent that is characterized by neutrophil-dominated airway inflammation due to intrinsic cellular abnormalities in the affected epithelial cells. A number of proinflammatory stimuli are responsible for aggravating inflammatory responses in CF bronchial epithelium. Two important host-derived factors with potent proinflammatory effects in CF are interleukin-1 (IL-1) and neutrophil elastase (NE). Microbial-derived factors also have importance in the CF lung, as a significant factor by which pulmonary inflammation is mediated in CF is by Pseudomonas aeruginosa infection. Pseudomonas antigens, including lipopolysaccharide (LPS), can exacerbate pulmonary inflammation in CF by exaggerating proinflammatory gene expression via Toll-like receptor (TLR) activation. TLRs belong to a family of proteins that can recognize and discriminate a diverse array of microbial antigens. Following their activation TLRs transduce intracellular signals that regulate proinflammatory gene expression. Intriguingly IL-1, NE and LPS all utilize the same intracellular signaling pathways to induce their effects. This review will summarise what is known regarding the roles of these important proinflammatory stimuli and their effects on CF epithelium and describe current and novel therapeutic strategies for the treatment of CF lung disease.

Keywords: interleukin-1, neutrophil elastase, lipopolysaccharide, cystic fibrosis, inflammation

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Article Details

VOLUME: 1
ISSUE: 1
Year: 2005
Page: [43 - 67]
Pages: 25
DOI: 10.2174/1573398052953640