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

Wyatt, Todd A.; Slager, Rebecca E.; DeVasure, Jane M.; Auvermann, Brent W.; Mulhern, Michael L.; Essen, Susanna G. Von; Mathisen, T.; Floreani, Anthony A.; Romberger, Debra J.

doi:10.1152/ajplung.00103.2007

Cited by 37 publications

(40 citation statements)

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“…PKCε and PKC␣ kinase activities were measured from the tracheas of the BALB/c mice as previously described (29). Briefly, the tracheas were homogenized in lysis buffer, sonicated, and centrifuged at 10,000 g for 30 min at 4°C.…”

Section: Methodsmentioning

confidence: 99%

Aging causes a slowing in ciliary beat frequency, mediated by PKCε

Bailey

Bonasera

Wilderdyke

et al. 2014

American Journal of Physiology-Lung Cellular and Molecular Phys

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The elderly are at much higher risk for developing pneumonia than younger individuals. Pneumonia is a leading cause of death and is the third most common reason for hospitalization in the elderly. One reason that elderly people may be more susceptible to pneumonia is a breakdown in the lung's first line of defense, mucociliary clearance. Cilia beat in a coordinated manner to propel out invading microorganisms and particles. Ciliary beat frequency (CBF) is known to slow with aging, however, little is known about the mechanism(s) involved. We compared the CBF in BALB/c and C57BL/6 mice aged 2, 12, and 24 mo and found that CBF diminishes with age. Cilia in the mice at age 12 and 24 mo retained their ability to be stimulated by the ␤2 agonist procaterol. To help determine the mechanism of ciliary slowing, we measured protein kinase C alpha and epsilon (PKC␣ and PKCε) activity. There were no activity differences in PKC␣ between the mice aged 2, 12, or 24 mo. However, we demonstrated a significantly higher PKCε activity in the mice at 12 and 24 mo than the in the mice 2 mo of age. The increase in activity is likely due to a nearly threefold increase in PKCε protein in the lung during aging. To strengthen the connection between activation of PKCε and ciliary slowing, we treated tracheas of mice at 2 mo with the PKCε agonist 8-[2-(2-pentylcyclopropylmethyl)-cyclopropyl]-octanoic acid (DCP-LA). We noted a similar decrease in baseline CBF, and the cilia remained sensitive to stimulation with ␤2 agonists. The mechanisms for the slowing of baseline CBF have not been previously determined. In this mouse model of aging we were able to show that decreases in CBF are related to an increase in PKCε activity. pneumonia; elderly; PKC epsilon; Sisson-Ammons video analysis (SAVA), lung; innate immunity; ␤2 agonists; DCP-LA FOR PEOPLE 65 AND OLDER, pneumonia is the seventh leading cause of death (12) and the third most common reason for hospitalization (18). The elderly are four times more likely to develop pneumonia than younger adults (9), and nearly 90% of deaths due to pneumonia occur in those 65 or older (6). People aged 85 and older have the highest risk of pneumonia, with a nearly three times greater risk than those aged 65-69 (8). Despite appropriate antibiotic therapy, the mortality of pneumonia in the elderly is higher than in younger populations (17). In fact, advancing age is independently associated with mortality (15). Little is known at the molecular level about how normal aging leads to an increased susceptibility to pneumonia and higher mortality.The lung is continuously exposed to the outside environment, and has a complex innate immune system to defend itself from microbial infection. The first line of defense is mucociliary clearance. The conducting airways of the lung are lined with ciliated airway epithelium. When foreign particles or microorganisms try to invade the airway epithelium, they are trapped in the mucus layer, and the cilia beat in a coordinated manner to remove the invading pathogens. Ciliary beatin...

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Section: Methodsmentioning

confidence: 99%

Aging causes a slowing in ciliary beat frequency, mediated by PKCε

Bailey

Bonasera

Wilderdyke

et al. 2014

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…To extend our in vitro bronchial epithelial cell observations that implicate PKC␣ and PKCε in modulating dust-induced inflammation (46), PKC␣ and PKCε activity were determined in whole lung tissue and isolated epithelial cells from murine trachea. These tissues were chosen because epithelial cells can be isolated from the trachea and provide insight into bronchial and alveolar epithelial cell responses, whereas whole lung tissue represents a multicellular organ response.…”

Section: Methodsmentioning

confidence: 99%

Intranasal organic dust exposure-induced airway adaptation response marked by persistent lung inflammation and pathology in mice

Poole¹,

Wyatt²,

Oldenburg³

et al. 2009

American Journal of Physiology-Lung Cellular and Molecular Phys

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108

258

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Animal models to study these mechanisms are limited. This study investigated the effects of single vs. repetitive dust-induced airway inflammation in mice by intranasal exposure method. Mice were exposed to swine facility dust extract (DE) or saline once and once daily for 1 and 2 wk. Dust exposure resulted in increased bronchoalveolar lavage fluid neutrophils and macrophages after single and repetitive exposures. Lavage fluid TNF␣, IL-6, keratinocyte chemoattractant, and macrophage inflammatory protein-2 were significantly increased after single and repetitive dust exposures, but were dampened in 2-wk dust-exposed mice compared with single exposure. Dust exposure induced PKC␣ and -ε activation in isolated tracheal epithelial cells but were dampened with repetitive exposures. Ex vivo stimulation of alveolar macrophages from 2-wk animals demonstrated reduced cytokine responsiveness and phagocytic ability. Significant lung pathology occurred with development of mixed mononuclear cellular aggregates (T and B lymphocytes, phagocytes) after repetitive dust exposure, a novel observation. Airway hyperresponsiveness to methacholine occurred after single dust exposure but resolved after 2 wk. Collectively, intranasal exposure to DE results in significant lung inflammatory and pathological responses marked by a modulated innate immune response to single and repetitive dust exposures that is associated with PKC activity.

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“…Acute and chronic exposures of experimental animals to animal facility dust are associated with recruitment of neutrophils and macrophages into the lung and lung pathology similar to that in humans exposed to animal facility dust (9,16,43). In vitro exposure of macrophages and lung epithelial cells to animal facility and agricultural dust extracts increases production of proinflammatory cytokines interleukin-6 (IL-6) and IL-8 (40,46,61).…”

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confidence: 99%