Protein kinase R, IκB kinase-β and NF-κB are required for human rhinovirus induced pro-inflammatory cytokine production in bronchial epithelial cells

2007 ◽  
Vol 44 (7) ◽  
pp. 1587-1597 ◽  
Author(s):  
Michael R. Edwards ◽  
Christopher A. Hewson ◽  
Vasile Laza-Stanca ◽  
Hoy-Tsun H. Lau ◽  
Naofumi Mukaida ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Epithelial Cells ◽  
Inflammatory Cytokine ◽  
Cytokine Production ◽  
Bronchial Epithelial Cells ◽  
Human Rhinovirus ◽  
Protein Kinase R ◽  
Bronchial Epithelial ◽  
Inflammatory Cytokine Production ◽  
Iκb Kinase

scholarly journals β2-Adrenergic agonists attenuate organic dust-induced lung inflammation

2016 ◽  
Vol 311 (1) ◽  
pp. L101-L110 ◽  
Author(s):  
Debra J. Romberger ◽  
Art J. Heires ◽  
Tara M. Nordgren ◽  
Jill A. Poole ◽  
Myron L. Toews ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Epithelial Cells ◽  
Lung Inflammation ◽  
Inflammatory Cytokine ◽  
Cytokine Production ◽  
Dust Exposure ◽  
Bronchial Epithelial ◽  
Inflammatory Cytokine Production ◽  
Neutrophil Influx ◽  
Pkc Activation

Agricultural dust exposure results in significant lung inflammation, and individuals working in concentrated animal feeding operations (CAFOs) are at risk for chronic airway inflammatory diseases. Exposure of bronchial epithelial cells to aqueous extracts of hog CAFO dusts (HDE) leads to inflammatory cytokine production that is driven by protein kinase C (PKC) activation. cAMP-dependent protein kinase (PKA)-activating agents can inhibit PKC activation in epithelial cells, leading to reduced inflammatory cytokine production following HDE exposure. β2-Adrenergic receptor agonists (β2-agonists) activate PKA, and we hypothesized that β2-agonists would beneficially impact HDE-induced adverse airway inflammatory consequences. Bronchial epithelial cells were cultured with the short-acting β2-agonist salbutamol or the long-acting β2-agonist salmeterol prior to stimulation with HDE. β2-Agonist treatment significantly increased PKA activation and significantly decreased HDE-stimulated IL-6 and IL-8 production in a concentration- and time-dependent manner. Salbutamol treatment significantly reduced HDE-induced intracellular adhesion molecule-1 expression and neutrophil adhesion to epithelial cells. Using an established intranasal inhalation exposure model, we found that salbutamol pretreatment reduced airway neutrophil influx and IL-6, TNF-α, CXCL1, and CXCL2 release in bronchoalveolar lavage fluid following a one-time exposure to HDE. Likewise, when mice were pretreated daily with salbutamol prior to HDE exposure for 3 wk, HDE-induced neutrophil influx and inflammatory mediator production were also reduced. The severity of HDE-induced lung pathology in mice repetitively exposed to HDE for 3 wk was also decreased with daily salbutamol pretreatment. Together, these results support the need for future clinical investigations to evaluate the utility of β2-agonist therapies in the treatment of airway inflammation associated with CAFO dust exposure.

scholarly journals cAMP-dependent protein kinase activation decreases cytokine release in bronchial epithelial cells

2014 ◽  
Vol 307 (8) ◽  
pp. L643-L651 ◽  
Author(s):  
Todd A. Wyatt ◽  
Jill A. Poole ◽  
Tara M. Nordgren ◽  
Jane M. DeVasure ◽  
Art J. Heires ◽  
...  
Keyword(s):  
Cell Migration ◽  
Protein Kinase ◽  
Epithelial Cells ◽  
Wound Repair ◽  
Bronchial Epithelial Cells ◽  
Dependent Protein Kinase ◽  
Bronchial Epithelial ◽  
Cyclic Monophosphate ◽  
Tnf Α ◽  
Dependent Protein

Lung injury caused by inhalation of dust from swine-concentrated animal-feeding operations (CAFO) involves the release of inflammatory cytokine interleukin 8 (IL-8), which is mediated by protein kinase C-ε (PKC-ε) in airway epithelial cells. Once activated by CAFO dust, PKC-ε is responsible for slowing cilia beating and reducing cell migration for wound repair. Conversely, the cAMP-dependent protein kinase (PKA) stimulates contrasting effects, such as increased cilia beating and an acceleration of cell migration for wound repair. We hypothesized that a bidirectional mechanism involving PKA and PKC regulates epithelial airway inflammatory responses. To test this hypothesis, primary human bronchial epithelial cells and BEAS-2B cells were treated with hog dust extract (HDE) in the presence or absence of cAMP. PKC-ε activity was significantly reduced in cells that were pretreated for 1 h with 8-bromoadenosine 3′,5′-cyclic monophosphate (8-Br-cAMP) before exposure to HDE ( P < 0.05). HDE-induced IL-6, and IL-8 release was significantly lower in cells that were pretreated with 8-Br-cAMP ( P < 0.05). To exclude exchange protein activated by cAMP (EPAC) involvement, cells were pretreated with either 8-Br-cAMP or 8-(4-chlorophenylthio)-2'- O-methyladenosine-3',5'-cyclic monophosphate (8-CPT-2Me-cAMP) (EPAC agonist). 8-CPT-2Me-cAMP did not activate PKA and did not reduce HDE-stimulated IL-6 release. In contrast, 8-Br-cAMP decreased HDE-stimulated tumor necrosis factor (TNF)-α-converting enzyme (TACE; ADAM-17) activity and subsequent TNF-α release ( P < 0.001). 8-Br-cAMP also blocked HDE-stimulated IL-6 and keratinocyte-derived chemokine release in precision-cut mouse lung slices ( P < 0.05). These data show bidirectional regulation of PKC-ε via a PKA-mediated inhibition of TACE activity resulting in reduced PKC-ε-mediated release of IL-6 and IL-8.

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