Differential effects of cytokines and corticosteroids on toll-like receptor 2 expression and activity in human airway epithelia

Audra A Winder; Christine Wohlford-Lenane; Todd E Scheetz; Brie N Nardy; Lori J Manzel; Dwight C Look; Paul B McCray Jr

doi:10.1186/1465-9921-10-96

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Differential effects of cytokines and corticosteroids on toll-like receptor 2 expression and activity in human airway epithelia

Journal article

Open access

Peer reviewed

Differential effects of cytokines and corticosteroids on toll-like receptor 2 expression and activity in human airway epithelia

Audra A Winder, Christine Wohlford-Lenane, Todd E Scheetz, Brie N Nardy, Lori J Manzel, Dwight C Look and Paul B McCray Jr

Respiratory research, Vol.10(1), pp.96-96

10/16/2009

DOI: 10.1186/1465-9921-10-96

PMCID: PMC2772856

PMID: 19835594

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Abstract

The recognition of microbial molecular patterns via toll-like receptors (TLRs) is critical for mucosal defenses. Using well-differentiated primary cultures of human airway epithelia, we investigated the effects of exposure of the cells to cytokines (TNF-alpha and IFN-gamma) and dexamethasone (dex) on responsiveness to the TLR2/TLR1 ligand Pam3CSK4. Production of IL-8, CCL20, and airway surface liquid antimicrobial activity were used as endpoints. Microarray expression profiling in human airway epithelia revealed that first response cytokines markedly induced TLR2 expression. Real-time PCR confirmed that cytokines (TNF-alpha and IFN-gamma), dexamethasone (dex), or cytokines + dex increased TLR2 mRNA abundance. A synergistic increase was seen with cytokines + dex. To assess TLR2 function, epithelia pre-treated with cytokines +/- dex were exposed to the TLR2/TLR1 ligand Pam3CSK4 for 24 hours. While cells pre-treated with cytokines alone exhibited significantly enhanced IL-8 and CCL20 secretion following Pam3CSK4, mean IL-8 and CCL20 release decreased in Pam3CSK4 stimulated cells following cytokines + dex pre-treatment. This marked increase in inflammatory gene expression seen after treatment with cytokines followed by the TLR2 ligand did not correlate well with NF-kappaB, Stat1, or p38 MAP kinase pathway activation. Cytokines also enhanced TLR2 agonist-induced beta-defensin 2 mRNA expression and increased the antimicrobial activity of airway surface liquid. Dex blocked these effects. While dex treatment enhanced TLR2 expression, co-administration of dex with cytokines inhibited airway epithelial cell responsiveness to TLR2/TLR1 ligand over cytokines alone. Enhanced functional TLR2 expression following exposure to TNF-alpha and IFN-gamma may serve as a dynamic means to amplify epithelial innate immune responses during infectious or inflammatory pulmonary diseases.

Ligands

Pseudomonas aeruginosa - immunology

Tumor Necrosis Factor-alpha - metabolism

Chemokine CCL20 - metabolism

Respiratory Mucosa - drug effects

Toll-Like Receptor 2 - genetics

Oligonucleotide Array Sequence Analysis

Lipopeptides - pharmacology

Epithelial Cells - drug effects

Humans

Interferon-gamma - metabolism

Listeria monocytogenes - immunology

RNA, Messenger - metabolism

Dexamethasone - pharmacology

Interleukin-1beta - metabolism

Respiratory Mucosa - immunology

Inflammation Mediators - metabolism

Toll-Like Receptor 2 - drug effects

Interleukin-8 - metabolism

Recombinant Proteins - metabolism

Cytokines - metabolism

Immunity, Innate - drug effects

Cells, Cultured

Adrenal Cortex Hormones - pharmacology

Escherichia coli - immunology

Gene Expression Profiling - methods

Toll-Like Receptor 2 - metabolism

Epithelial Cells - immunology

Details

Title: Subtitle: Differential effects of cytokines and corticosteroids on toll-like receptor 2 expression and activity in human airway epithelia
Creators: Audra A Winder - Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, IA, USA. audra.winder@marshfieldclinic.org
Christine Wohlford-Lenane
Todd E Scheetz
Brie N Nardy
Lori J Manzel
Dwight C Look
Paul B McCray Jr
Resource Type: Journal article
Publication Details: Respiratory research, Vol.10(1), pp.96-96
DOI: 10.1186/1465-9921-10-96
PMID: 19835594
PMCID: PMC2772856
NLM abbreviation: Respir Res
ISSN: 1465-993X
eISSN: 1465-993X
Publisher: England
Grant note: HL-075559 / NHLBI NIH HHS HL-082505 / NHLBI NIH HHS P30 DK-54759 / NIDDK NIH HHS P50 HL-61234 / NHLBI NIH HHS T32AI007343 / NIAID NIH HHS N01 AI-30040 / NIAID NIH HHS P30 DK054759 / NIDDK NIH HHS
Language: English
Date published: 10/16/2009
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Electrical and Computer Engineering; Microbiology and Immunology; Pulmonary Medicine; Stead Family Department of Pediatrics; Internal Medicine; Ophthalmology and Visual Sciences
Record Identifier: 9983979970102771

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