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

Autor: Lori J. Manzel, Paul B. McCray, Dwight C. Look, Christine L. Wohlford-Lenane, Brie N Nardy, Audra A Winder, Todd E. Scheetz
Jazyk: angličtina
Rok vydání: 2009
Předmět:
Pulmonary and Respiratory Medicine
p38 mitogen-activated protein kinases
Interleukin-1beta
Respiratory Mucosa
Pharmacology
Biology
Ligands
Dexamethasone
03 medical and health sciences
Interferon-gamma
Lipopeptides
0302 clinical medicine
Adrenal Cortex Hormones
Escherichia coli
Humans
Interleukin 8
RNA
Messenger
Receptor
Cells
Cultured
030304 developmental biology
Oligonucleotide Array Sequence Analysis
lcsh:RC705-779
0303 health sciences
Toll-like receptor
Innate immune system
Chemokine CCL20
Tumor Necrosis Factor-alpha
Research
Gene Expression Profiling
Interleukin-8
Epithelial Cells
lcsh:Diseases of the respiratory system
Molecular biology
Listeria monocytogenes
Immunity
Innate
Recombinant Proteins
Toll-Like Receptor 2
3. Good health
CCL20
TLR2
Pseudomonas aeruginosa
Cytokines
Tumor necrosis factor alpha
Inflammation Mediators
030215 immunology
Zdroj: Respiratory Research, Vol 10, Iss 1, p 96 (2009)
Respiratory Research
ISSN: 1465-9921
Popis: Background The recognition of microbial molecular patterns via Toll-like receptors (TLRs) is critical for mucosal defenses. Methods Using well-differentiated primary cultures of human airway epithelia, we investigated the effects of exposure of the cells to cytokines (TNF-α and IFN-γ) 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. Results Microarray expression profiling in human airway epithelia revealed that first response cytokines markedly induced TLR2 expression. Real-time PCR confirmed that cytokines (TNF-α and IFN-γ), 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-κB, 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. Conclusion 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-α and IFN-γ may serve as a dynamic means to amplify epithelial innate immune responses during infectious or inflammatory pulmonary diseases.
Databáze: OpenAIRE
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