Release and actions of inhibitory prostaglandins from canine tracheal epithelium

McGrogan, I.; Daniel, E. E.

doi:10.1139/y96-113

Cited by 9 publications

(1 citation statement)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Epithelium has been considered as one of the major sources of prostanoid production in the airways (21,29). However, our study shows that removal of epithelium from guinea pig tracheas did not induce an expected reduction of prostanoid release.…”

Section: Discussioncontrasting

confidence: 60%

Reduced spontaneous relaxation in immature guinea pig airway smooth muscle is associated with increased prostanoid release

Wang

Pozzato²,

Turato³

et al. 2008

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

Airway smooth muscle (ASM) from infant guinea pigs has less spontaneous relaxation during stimulation than ASM from adults. Inhibition of cyclooxygenase (COX), which catalyzes the production of prostanoids, increases this relaxation in infant ASM and abolishes age differences, thus suggesting that prostanoids reduce relaxation in infant ASM. In this study, we investigated whether leukotrienes are also involved in reducing spontaneous relaxation; whether the two COX isoforms, COX-1 and COX-2, differentially regulate spontaneous relaxation; and whether prostanoid release is developmentally regulated in guinea pig ASM. In different age groups, we measured relaxation during and after electrical stimulation in tracheal strips as well as prostanoid release from tracheal segments. Relaxation was studied in the absence and in the presence of a lipoxygenase inhibitor, a cysteinyl leukotriene receptor-1 antagonist, a COX-1 inhibitor, or a COX-2 inhibitor. We found that inhibition of lipoxygenase or cysteinyl leukotriene receptor-1 antagonism did not increase spontaneous relaxation at any age, thus excluding a role for leukotrienes in this phenomenon. Inhibition of COX-2, but not COX-1, promoted spontaneous relaxation. The basal release of prostanoids was more abundant in tissue from infant animals and decreased significantly with age. Thromboxane B2 was the most abundant metabolite released at all ages. Electrical stimulation and epithelium removal did not affect the age difference in prostanoid release. We conclude that increased basal prostanoid release contributes to the reduced spontaneous relaxation in immature guinea pig ASM compared with older animals. By regulating ASM relaxation, prostanoids may play a role in the airway hyperresponsiveness at a young age.

show abstract

Section: Discussioncontrasting

confidence: 60%

Reduced spontaneous relaxation in immature guinea pig airway smooth muscle is associated with increased prostanoid release

Wang

Pozzato²,

Turato³

et al. 2008

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

show abstract

An epithelial-derived factor inhibits contraction in canine perfused bronchial segments

McParland

Johnson

Armour

et al. 2000

European Journal of Pharmacology

View full text Add to dashboard Cite

Bacterial Challenge Stimulates Formation of Arachidonic Acid Metabolites by Human Keratinocytes and Neutrophils In Vitro

Eberhard

Jepsen

Pohl

et al. 2002

Clin Vaccine Immunol

View full text Add to dashboard Cite

Although the interactions of bacteria with keratinocytes induce the synthesis of various mediators, the capability of epithelial cells to form arachidonic acid mediators has not been studied, and therefore the first part of this study was initiated. The complex mixture of epithelium-derived mediators suggests that chemoattraction is not their only effect on neutrophils and that they may also affect neutrophil mediator synthesis. The effect of epithelium-derived mediators on neutrophil eicosanoide synthesis was evaluated in the second part of this study. We incubated human keratinocytes with human-pathogenic bacteria for 2 h and harvested the supernatants after 4, 6, 10, and 18 h of culture. Subsequently, the supernatants were coincubated for 5 min with human neutrophils with or without arachidonic acid. The formation of the arachidonic acid metabolites prostaglandin E 2 (PGE 2 ), leukotriene B 4 (LTB 4 ), 12-hydroxyeicosatetraenoic acid (12-HETE), and 15-HETE in keratinocytes and neutrophils was measured by reverse-phase high-pressure liquid chromatography. We demonstrated for the first time that keratinocytes produced significant amounts of LTB 4 and 12-HETE 4 to 6 h after bacterial challenge. Upon stimulation with epithelial supernatants, neutrophils produced significant amounts of PGE 2 , LTB 4 , 12-HETE, and 15-HETE throughout the observation period of 18 h, with a maximum synthesis by supernatants harvested 4 to 10 h after bacterial infection. The results of the study suggest that arachidonic acid mediator formation by epithelial cells following bacterial challenge may act as an early inflammatory signal for the initiation of the immune response. The epithelial supernatants were capable of inducing the formation of arachidonic acid mediators by neutrophils, which may have further regulatory effects on the immune response.Although the mechanisms controlling inflammation are poorly understood, the release of pro-and anti-inflammatory mediators plays a central role in the initiation, perpetuation, and limitation of this process. Bacterial infection is an important stimulus for the synthesis of inflammatory mediators in human tissues. Epithelial cells are the first cell line that interacts with bacteria and causes the increased expression and secretion of a number of cytokines and proinflammatory mediators (24). These mediators are characterized by their ability to chemoattract and activate polymorphonuclear leukocytes (PMNs), suggesting that an important function of epithelial cells is to initiate the mucosal influx of PMNs. The arachidonic acid metabolites leukotriene B 4 (LTB 4 ), 12-hydroxyeicosatetraenoic acid (12-HETE), and 15-HETE regulate PMN functions, including chemotaxis (6, 17, 33, 42), degranulation (13,38,41), and adherence (7), which may indicate the critical role of these metabolites for early events in inflammation.The synthesis of various inflammatory mediators by keratinocytes upon bacterial infection suggests that the induction of chemokinesis is not the only functional change that is induce...

show abstract

Release and actions of inhibitory prostaglandins from canine tracheal epithelium

Cited by 9 publications

References 10 publications

Reduced spontaneous relaxation in immature guinea pig airway smooth muscle is associated with increased prostanoid release

Reduced spontaneous relaxation in immature guinea pig airway smooth muscle is associated with increased prostanoid release

An epithelial-derived factor inhibits contraction in canine perfused bronchial segments

Bacterial Challenge Stimulates Formation of Arachidonic Acid Metabolites by Human Keratinocytes and Neutrophils In Vitro

Contact Info

Product

Resources

About