Prostanoid receptor expression by human airway smooth muscle cells and regulation of the secretion of granulocyte colony-stimulating factor

Abstract

receptor expression by human airway smooth muscle cells and regulation of the secretion of granulocyte colony-stimulating factor. Am J Physiol Lung Cell Mol Physiol 288: L238 -L250, 2005; doi:10.1152/ ajplung.00313.2004.-The prostanoid receptors on human airway smooth muscle cells (HASMC) that augment the release by IL-1␤ of granulocyte colony-stimulating factor (G-CSF) have been characterized and the signaling pathway elucidated. PCR of HASM cDNA identified products corresponding to EP 2, EP3, and EP4 receptor subtypes. These findings were corroborated at the protein level by immunocytochemistry. IL-1␤ promoted the elaboration of G-CSF, which was augmented by PGE2. Cicaprost (IP receptor agonist) was approximately equiactive with PGE2, whereas PGD2, PGF2␣, and U-46619 (TP receptor agonist) were over 10-fold less potent. Neither SQ 29,548 nor BW A868C (TP and DP1 receptor antagonists, respectively) attenuated the enhancement of G-CSF release evoking any of the prostanoids studied. With respect to PGE2, the EP receptor agonists 16,16-dimethyl PGE2 (nonselective), misoprostol (EP2/EP3 selective), 17-phenyl--trinor PGE2 (EP1 selective), ONO-AE1-259, and butaprost (both EP2 selective) were full agonists at enhancing G-CSF release. AH 6809 (10 M) and L-161,982 (2 M), which can be used in HASMC as selective EP2 and EP4 receptor antagonists, respectively, failed to displace to the right the PGE2 concentrationresponse curve that described the augmented G-CSF release. In contrast, AH 6809 and L-161,982 in combination competitively antagonized PGE2-induced G-CSF release. Augmentation of G-CSF release by PGE 2 was mimicked by 8-BrcAMP and abolished in cells infected with an adenovirus vector encoding an inhibitor protein of cAMP-dependent protein kinase (PKA). These data demonstrate that PGE2 facilitates G-CSF secretion from HASMC through a PKAdependent mechanism by acting through EP2 and EP4 prostanoid receptors and that effective antagonism is realized only when both subtypes are blocked concurrently.cAMP-dependent protein kinase; human airway smooth muscle; granulocyte colony-stimulating factor; prostanoid receptors; airway inflammation

Moraxella catarrhalis induces ERK- and NF- B-dependent COX-2 and prostaglandin E2 in lung epithelium

“…The secretion of several cytokines involved in the cellular inflammatory and reparative processes are known to be modulated by PGE 2 . Interestingly, PGE 2 has been shown to increase the secretion of G-CSF in human airway smooth muscle cells [27]. Additionally, the ability of PGE 2 to downregulate the production of important cytokines, such as IL-8, MCP-1 and GM-CSF, which are significantly involved in the recruitment of inflammatory cells has also been reported [11,27].…”

“…Interestingly, PGE 2 has been shown to increase the secretion of G-CSF in human airway smooth muscle cells [27]. Additionally, the ability of PGE 2 to downregulate the production of important cytokines, such as IL-8, MCP-1 and GM-CSF, which are significantly involved in the recruitment of inflammatory cells has also been reported [11,27]. MONTUSCHI et al [12] demonstrated that exhaled PGE 2 was increased in patients with stable COPD and suggested this to be a mechanism counteracting lung inflammation in COPD.…”

The Prostanoid EP4 Receptor and Its Signaling Pathway

“…EP4 is highly expressed in airway smooth muscle cells, pulmonary fibroblasts, and smooth muscle cells of the pulmonary vein. In particular, together with the EP2 receptor, EP4 transcripts and proteins are abundantly expressed in human airway smooth muscle cells (Bradbury et al, 2005;Clarke et al, 2005;Mori et al, 2011;Benyahia et al, 2012). It is also known that EP4 activation causes potent relaxation in human and rat bronchial preparations (Lydford and McKechnie, 1994;Benyahia et al, 2012).…”

E-Ring 8-Isoprostanes Are Agonists at EP2- and EP4-Prostanoid Receptors on Human Airway Smooth Muscle Cells and Regulate the Release of Colony-Stimulating Factors by Activating cAMP-Dependent Protein Kinase

“…It is noteworthy that these results are not peculiar to 8-iso-PGE 1 and 8-iso-PGE 2 . On HASM cells, we have found that PGE 2 , butaprost (EP 2 -receptor agonist), and PGE 1 -OH also augment G-CSF release together with a number of other ligands (e.g., 16,16-dimethyl-PGE 2 , ONO-AE1-259, and misoprostol) that have selectivity for the EP 2 -and/or EP 4 -receptor subtype (Clarke et al, 2005). Furthermore, although butaprost-and PGE 1 -OH-induced G-CSF secretion was antagonized by AH 6809 and L-161,982, respectively, with the expected affinity, the same response evoked by PGE 2 was insensitive to these antagonists unless they were deployed simultaneously (Clarke et al, 2005).…”

“…Herein, we describe an anti-and proinflammatory effect of E-ring 8-isoprostanes on the synthetic capacity of HASM cells and have identified the receptors and signal transduction pathways involved. In particular, the effect of 8-iso-PGE 1 and 8-iso-PGE 2 has been compared with F␣-ring isoprostanes on the secretion of two colony-stimulating factors (CSFs), G-CSF and GM-CSF, which have previously been shown to be modulated by E-series prostaglandins (Clarke et al, 2001(Clarke et al, , 2004a(Clarke et al, , 2005. These cytokines, discovered in the 1960s, were selected for study because they are essential for the differentiation, proliferation, and survival of bone marrow-derived hematopoietic stem cells and have been implicated in the pathogenesis of asthma and chronic obstructive pulmonary disease where they enhance in the airways the activation and survival of eosinophils, neutrophils, and cells of the monocyte/macrophage lineage (Metcalf, 1985).…”