Type

Journal Article

Authors

Noel G McElvaney
Shane J O'Neill
Andrew G Bowie
Clifford C Taggart
Catherine M Greene
Tomás P Carroll

Subjects

Biochemistry

Topics
immunology membrane glycoproteins interleukin 8 biosynthesis p38 mitogen activated protein kinases tirap protein human inflammation interleukin 1 receptor associated kinases a46r protein vaccinia virus viral proteins leukocyte elastase blotting western epithelial cells toll like receptor 4 receptors interleukin 1 myeloid differentiation factor 88 transfection bronchi cell line virology adaptor proteins signal transducing myd88 protein human protein kinases metabolism a52r protein vaccinia virus humans gene expression regulation gene expression receptors immunologic antigens differentiation tlr4 protein human interleukin 1

Viral inhibition of IL-1- and neutrophil elastase-induced inflammatory responses in bronchial epithelial cells. (2005)

Abstract Previously, we elucidated the intracellular mechanisms by which neutrophil elastase (NE) up-regulates inflammatory gene expression in bronchial epithelial cells. In this study, we examine the effects of both IL-1 and NE on inflammatory gene expression in 16HBE14o- bronchial epithelial cells and investigate approaches to abrogate these inflammatory responses. IL-1 induced IL-8 protein production in time- and dose-dependent fashions, an important observation given that IL-8 is a potent neutrophil chemoattractant and a key inflammatory mediator. IL-1 and NE were shown to activate the p38 MAPK pathway in 16HBE14o- cells. Western blot analysis demonstrated IL-1R-associated kinase 1 (IRAK-1) degradation in response to stimulation with both IL-1 and NE. In addition, the expression of dominant negative IRAK-1 (IRAK-1delta), IRAK-2delta, or IRAK-4delta inhibited IL-1- and NE-induced NF-kappaB-linked reporter gene expression. Dominant negative versions of the intracellular adaptor proteins MyD88 (MyD88delta) and MyD88 adaptor-like (Mal P/H) abrogated NE-induced NF-kappaB reporter gene expression. In contrast, only MyD88delta was found to inhibit IL-1-induced NF-kappaB reporter activity. We also investigated the vaccinia virus proteins, A46R and A52R, which have been shown to antagonize IL-1 signaling. Transfection with A46R or A52R cDNA inhibited IL-1- and NE-induced NF-kappaB and IL-8R gene expression and IL-8 protein production in primary and transformed bronchial epithelial cells. Furthermore, cytokine array studies demonstrated that IL-1 and NE can up-regulate the expression of IL-6, oncostatin M, epithelial cell-derived neutrophil activating peptide-78, growth-related oncogene family members, vascular endothelial growth factor, and GM-CSF, with induction of these proteins inhibited by the viral proteins. These findings identify vaccinia virus proteins as possible therapeutic agents for the manifestations of several inflammatory lung diseases.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

Noel G McElvaney, Shane J O'Neill, Andrew G Bowie, Clifford C Taggart, Catherine M Greene, Tomás P Carroll

Experts in our system

1
Noel G McElvaney
Royal College of Surgeons in Ireland
Total Publications: 194
 
2
Shane J O'Neill
Royal College of Surgeons in Ireland
Total Publications: 84
 
3
Clifford C Taggart
Royal College of Surgeons in Ireland
Total Publications: 54
 
4
Catherine M Greene
Royal College of Surgeons in Ireland
Total Publications: 150
 
5
Tomás P Carroll
Royal College of Surgeons in Ireland
Total Publications: 26