Protein Kinase C-α Mediates Cigarette Smoke Extract- and Complement Factor 5a-Stimulated Interleukin-8 Release in Human Bronchial Epithelial Cells

Kashyap, Ravindra; Floreani, Anthony A.; Heires, Art J.; Sanderson, Sam D.; Wyatt, Todd A.

doi:10.2310/6650.2002.33517

Cited by 19 publications

(17 citation statements)

References 34 publications

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“…Clearly, this isoenzyme plays many roles in airway epithelial signaling depending on the specific cell type and stimulatory agent involved. Adding to this complexity is the observation that interleukin release can be mediated by other PKC isoforms, such as the stimulation of cigarette smoke-induced IL-8 release via PKC␣ (11). Due to the nature of auto-downregulation in response to activation of PKC, it is not surprising that multiple PKC isoforms would demonstrate overlapping functions.…”

Section: Discussionmentioning

confidence: 96%

Feedlot dust stimulation of interleukin-6 and -8 requires protein kinase Cε in human bronchial epithelial cells

Wyatt¹,

Slager²,

DeVasure³

et al. 2007

American Journal of Physiology-Lung Cellular and Molecular Phys

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Individuals exposed to dusts from concentrated animal feeding operations report increased numbers of respiratory tract symptoms, and bronchoalveolar lavage samples from such individuals demonstrate elevated lung inflammatory mediators, including interleukin (IL)-8 and IL-6. We previously found that exposure of bronchial epithelial cells to hog barn dusts resulted in a protein kinase C (PKC)-dependent increase in IL-6 and IL-8 release. We hypothesized that cattle feedlot dusts would also generate bronchial epithelial interleukin release in vitro. To test this, we used interleukin ELISAs and direct PKC isoform assays. We found that a dust extract from cattle feedlots [feedlot dust extract (FLDE)] augments PKC activity of human bronchial epithelial cells in vitro. A 5-10% dilution of FLDE stimulated a significant release of IL-6 and IL-8 at 6-24 h in a PKC-dependent manner vs. control medium-treated cells. An increase in PKCalpha activity was observed with 1 h of FLDE treatment, and PKCepsilon activity was elevated at 6 h of FLDE exposure. The PKCalpha inhibitor, Gö-6976, did not inhibit FLDE-stimulated IL-8 and IL-6 release. However, the PKCepsilon inhibitor, Ro 31-8220, effectively inhibited FLDE-stimulated IL-8 and IL-6 release. Inhibition of FLDE-stimulated IL-6 and IL-8 was confirmed in a dominant-negative PKCepsilon-expressing BEAS-2B cell line but not observed in a PKCalpha dominant negative BEAS-2B cell line. These data support the hypothesis that FLDE exposure stimulates bronchial epithelial IL-8 and IL-6 release via a PKCepsilon-dependent pathway.

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Section: Discussionmentioning

confidence: 96%

Feedlot dust stimulation of interleukin-6 and -8 requires protein kinase Cε in human bronchial epithelial cells

Wyatt¹,

Slager²,

DeVasure³

et al. 2007

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…PKC family members are activated in response to mitogens, inflammatory stimuli and stress and play important roles in a variety of cellular functions including cell metabolisms, gene expression, mitogenesis, proliferation, differentiation, tumor promotion and apoptosis (Brodie and Blumberg, 2003;Jackson and Foster, 2004;Yoshida et al, 2002). Accumulating reports have indicated that protein kinase Cs (PKCs) contribute to IL-8 production in a variety of cells (Kashyap et al, 2002;Wyatt et al, 2001). Recent studies supported that PKCδ, one of the novel PKCs, mediates up-regulation of inflammationrelated proteins such as TNF-α, IL-1β, IL-8, and ICAM-1 in epithelial cells, endothelial cells, and monocytes (Kontny et al, 2000;Rahman et al, 2001;Vallee et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Involvement of protein kinase Cδ in iron chelator-induced IL-8 production in human intestinal epithelial cells

Choi

Lee

et al. 2007

Life Sciences

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“…We chose to inhibit ERK, c-src tyrosine kinase, and protein kinase C pathways because of their involvement in MMP expression (21)(22)(23). Northern blot analysis showed that 24-h treatment with 5% CSE alone increased MMP-1 mRNA in SAECs (Fig.…”

Section: Cse Increases Mmp-1 In Airway Epithelialmentioning

confidence: 99%

Extracellular Regulated Kinase/Mitogen Activated Protein Kinase Is Up-regulated in Pulmonary Emphysema and Mediates Matrix Metalloproteinase-1 Induction by Cigarette Smoke

Mercer

Kolesnikova

Sonett

et al. 2004

Journal of Biological Chemistry

158

172

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The interstitial collagenase matrix metalloproteinase-1 (MMP-1) is up-regulated in the lung during pulmonary emphysema. The mechanisms underlying this aberrant expression are poorly understood. Although cigarette smoking is the predominant cause of emphysema, only 15-20% of smokers develop the disease. To define the signaling pathways activated by smoke and to identify molecules responsible for emphysema-associated MMP-1 expression, we performed several in vitro and in vivo experiments. In this study, we showed that cigarette smoke directly induced MMP-1 mRNA and protein expression and increased the collagenolytic activity of human airway cells. Treatment with various chemical kinase inhibitors revealed that this response was dependent on the extracellular regulated kinase-1/2 (ERK) mitogen activated protein kinase pathway. Cigarette smoke increased phosphorylation of residues Thr-202 and Tyr-204 of ERK in airway lining cells and alveolar macrophages in mice at 10 days and 6 months of exposure. Moreover, analysis of lung tissues from emphysema patients revealed significantly increased ERK activity compared with lungs of control subjects. This ERK activity was evident in airway lining and alveolar cells. The identification of active ERK in the lungs of emphysema patients and the finding that induction of MMP-1 by cigarette smoke in pulmonary epithelial cells is ERKdependent reveal a molecular mechanism and potential therapeutic target for excessive matrix remodeling in smokers who develop emphysema.

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Protein Kinase C-α Mediates Cigarette Smoke Extract- and Complement Factor 5a-Stimulated Interleukin-8 Release in Human Bronchial Epithelial Cells

Abstract: Collectively, these data suggest that PKC activators in addition to CSE augment C5a-stimulated IL-8 release from HBEC and that CSE and C5a stimulate IL-8 release in HBEC by activating the calcium-dependent PKCalpha isoform.

Cited by 19 publications

References 34 publications

Feedlot dust stimulation of interleukin-6 and -8 requires protein kinase Cε in human bronchial epithelial cells

Feedlot dust stimulation of interleukin-6 and -8 requires protein kinase Cε in human bronchial epithelial cells

Involvement of protein kinase Cδ in iron chelator-induced IL-8 production in human intestinal epithelial cells

Extracellular Regulated Kinase/Mitogen Activated Protein Kinase Is Up-regulated in Pulmonary Emphysema and Mediates Matrix Metalloproteinase-1 Induction by Cigarette Smoke

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