Induction of eotaxin expression and release from human airway smooth muscle cells by IL‐1β and TNFα: effects of IL‐10 and corticosteroids

Chung, Kian Fan; Patel, Hema J; Fadlon, Emma; Rousell, Jonathan; Haddad, El-Bdaoui; Jose, Peter J.; Mitchell, Jane A.; Belvisi, Maria G.

doi:10.1038/sj.bjp.0702660

Cited by 96 publications

(70 citation statements)

References 29 publications

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“…5-oxo-ETE seems to be an intermediate chemoattractant as it down-regulates the migration of eosinophils to PGD 2 , but enhances their chemotaxis to eotaxin. By doing so, 5-oxo-ETE might divert the migrating eosinophils from the source of PGD 2 (e.g., mast cells) and further accelerate them towards a third chemoattractant, eotaxin, released from end-point targets, such as smooth muscle cells or the epithelium [39][40][41]. Hence, eotaxin could serve as an end-point chemoattractant also causing degranulation of eosinophils [30].…”

Section: Discussionmentioning

confidence: 99%

Hierarchy of eosinophil chemoattractants: role of p38 mitogen‐activated protein kinase

et al. 2006

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Several chemoattractants can regulate the recruitment of eosinophils to sites of inflammation, but the hierarchy among them is unknown. We observed here that eosinophil chemotaxis towards eotaxin or 5-oxo-6,8,11,14-eicosatetraenoic acid (5-oxo-ETE) was amplified up to sixfold in the presence of prostaglandin (PG) D 2 . This effect was only seen in eosinophils, and not in neutrophils or basophils. Pretreatment with the chemoattractant receptor-homologous molecule expressed on TH2 cells (CRTH2) antagonist ramatroban prevented the PGD 2 enhancement of eosinophil migrations. In contrast, eotaxin or 5-oxo-ETE inhibited the migration of eosinophils towards PGD 2 . 5-oxo-ETE enhanced the chemotaxis to eotaxin, while eotaxin had no effect on 5-oxo-ETE-induced migration. 5-oxo-ETE induced the phosphorylation of p38 mitogenactivated protein kinase, and inhibition of p38 mitogen-activated protein kinase by SB-202190 converted the effect of 5-oxo-ETE on the chemotaxis to PGD 2 from inhibition to enhancement. The presence of blood or plasma markedly decreased the sensitivity of eosinophils to eotaxin or 5-oxo-ETE, while responses to PGD 2 were unaltered. In conclusion, PGD 2 might be an initial chemoattractant, since it maintains its potency in the circulation and augments the responsiveness of eosinophils to other chemoattractants. In contrast, eotaxin seems to be an end-point chemoattractant, since it has reduced efficacy in blood and is capable of down-modulating eosinophil responsiveness to other chemoattractants. IntroductionAccumulation of eosinophils at sites of allergic reactions, such as eczema or asthma, is associated with tissue injury and lung dysfunction [1]. It has been shown recently that asthmatic patients that received treatment based on eosinophil counts in sputum had significantly fewer severe asthma exacerbations than patients treated according to standard management therapy [2]. Moreover, genetically modified mice lacking eosinophils are protected against allergen-induced lung injury and asthma [3,4].Although several chemoattractants can mediate eosinophil recruitment, none of them could be identified so far as a predominating factor governing eosinophil infiltration, suggesting a co-operative action of multiple chemoattractants in disease. Among these are the CC-chemokines, such as eotaxin, RANTES, or MCP-4 acting through the chemokine receptor CCR3 [5,6]. Prostaglandin (PG) D 2 , a major mast cell mediator released during the allergic response [7] might be of particular importance, since PGD 2 is capable of inducing the chemotaxis of eosinophils, basophils and Th2-type * These authors contributed equally to this study. T cells via a novel receptor, chemoattractant receptorhomologous molecule expressed on TH2 cells (CRTH2) [8,9]. Besides chemotaxis, we have shown that activation of CRTH2 also causes eosinophil respiratory burst and the release of eosinophils from the bone marrow [10]. In vivo, PGD 2 can induce pulmonary eosinophilia [11], and a significant contribution of PGD 2 to the late phase allergi...

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Section: Discussionmentioning

confidence: 99%

Hierarchy of eosinophil chemoattractants: role of p38 mitogen‐activated protein kinase

et al. 2006

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“…IL-8, RAN-TES, and eotaxin production by human ASMC is induced by TNF-␣ but not IFN-␥. Furthermore, although IFN-␥ potentiates TNF-␣-induced RANTES release, it has no synergistic effects on TNF-␣-induced IL-8 or eotaxin release (11,35,36,51). Thus the relative presence or absence of IFN-␥ and TNF-␣ in the inflammatory milieu may direct the pattern of ASMC chemokine synthesis and hence the type of inflammatory cells recruited.…”

Section: Discussionmentioning

confidence: 99%

Fractalkine/CX₃CL1 production by human airway smooth muscle cells: induction by IFN-γ and TNF-α and regulation by TGF-β and corticosteroids

Sukkar

Issa

Xie

et al. 2004

American Journal of Physiology-Lung Cellular and Molecular Phys

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mokine synthesis by airway smooth muscle cells (ASMC) may be an important process underlying inflammatory cell recruitment in airway inflammatory diseases such as asthma and chronic obstructive pulmonary disease (COPD). Fractalkine (FKN) is a recently described CX 3C chemokine that has dual functions, serving as both a cell adhesion molecule and a chemoattractant for monocytes and T cells, expressing its unique receptor, CX3CR1. We investigated FKN expression by human ASMC in response to the proinflammatory cytokines IL-1␤, TNF-␣, and IFN-␥, the T helper 2-type cytokines IL-4, IL-10, and IL-13, and the fibrogenic cytokine transforming growth factor (TGF)-␤. Neither of these cytokines alone had any significant effect on ASMC FKN production. Combined stimulation with IFN-␥ and TNF-␣ induced FKN mRNA and protein expression in a time-and concentration-dependent manner. TGF-␤ had a significant inhibitory effect on cytokine-induced FKN mRNA and protein expression. Dexamethasone (10 Ϫ8 -10 Ϫ6 M) significantly upregulated cytokineinduced FKN mRNA and protein expression. Finally, we used selective inhibitors of the mitogen-activated protein kinases c-Jun NH2-terminal kinase (JNK) (SP-610025), p38 (SB-203580), and extracellular signal-regulated kinase (PD-98095) to investigate their role in FKN production. SP-610025 (25 M) and SB-203580 (20 M), but not PD-98095, significantly attenuated cytokine-induced FKN protein synthesis. IFN-␥-and TNF-␣-induced JNK phosphorylation remained unaltered in the presence of TGF-␤ but was inhibited by dexamethasone, indicating that JNK is not involved in TGF-␤-or dexamethasone-mediated regulation of FKN production. In summary, FKN production by human ASMC in vitro is regulated by inflammatory and anti-inflammatory factors. chemokine; airway inflammation; asthma; chronic obstructive pulmonary disease THERE IS NOW SUBSTANTIAL EVIDENCE suggesting that airway smooth muscle cells (ASMC), by virtue of their immunomodulatory functions, may be involved in regulating airway inflammatory responses in diseases such as asthma and chronic obstructive pulmonary disease (COPD). ASMC express adhesion molecules and synthesize many cytokines and chemokines such as granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-8, eotaxin, and RANTES. These mediators are critically implicated in the recruitment, survival, and activation of key effector cells, such as eosinophils, neutrophils, and T lymphocytes, in asthma and COPD (10).Fractalkine (FKN), also known as CX 3 C ligand 1 (CX 3 CL1), is a novel chemokine belonging to the CX 3 C chemokine family. FKN is a multidomain molecule expressed on the cell surface and consists of a transmembrane region and a heavily glycosylated mucin-like stalk that extends from the cell surface, holding the chemokine domain at its tip (5). FKN also exists as a soluble glycoprotein that is generated by proteolytic cleavage of the full-length molecule at a membrane-proximal site (27,32,55). The physiological relevance of membrane and soluble FKN is not known; however, it is cu...

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“…The T-helper (Th)-2 T-cell derived cytokines, IL-4, IL-10 and IL-13, as well as dexamethasone inhibited RANTES mRNA and protein expression. The more selective eosinophil chemoattractant, eotaxin, is also expressed in human airway smooth muscle cells stimulated by IL-1b or TNFa [31,32]. Both IL-1b and TNFa-induced release of eotaxin was not inhibited by corticosteroids, in contrast to the release of RANTES [31].…”

Section: Chemokinesmentioning

confidence: 98%

“…The more selective eosinophil chemoattractant, eotaxin, is also expressed in human airway smooth muscle cells stimulated by IL-1b or TNFa [31,32]. Both IL-1b and TNFa-induced release of eotaxin was not inhibited by corticosteroids, in contrast to the release of RANTES [31]. The eosinophil chemoattractant activity of stimulated airway smooth muscle supernatants appears to be predominantly accounted for by RANTES and eotaxin [30,32].…”

Section: Chemokinesmentioning

confidence: 99%

Airway smooth muscle cells: contributing to and regulating airway mucosal inflammation?

Chung

2000

Eur Respir J

130

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In addition to its contractile properties, airway smooth muscle may contribute to the pathogenesis of asthma by increased proliferation, and by the expression and secretion of pro‐inflammatory cytokines and mediators. Studies of airway smooth muscle cells in culture have shown that many mitogenic mediators can induce proliferation, and that these may therefore, contribute to the increase in airway smooth muscle mass observed in asthma. Other mechanisms for airway smooth muscle proliferation include the interaction with inflammatory cells such as T‐cells and eosinophils. Airway smooth muscle cells may also be a source of inflammatory mediators and cytokines, in particular chemokines, thus implicating airway smooth muscle cells as contributors to the inflammatory mechanisms of asthma. The pro‐activating signals for converting airway smooth muscle cells into a proliferative and secretory cell in asthma are unknown, but may include viruses and immunoglobulin E. Airway smooth muscle contractility may also be altered in response to inflammation. Airway smooth muscle cells may play an important interactive role with inflammatory and other structural cells, contributing to inflammation, injury and repair of the airways. Such a recognition makes it imperative to consider the airway smooth muscle as a target of therapeutic drugs for suppressing not only the contractile but also the proliferative and secretory effects of asthma.

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Induction of eotaxin expression and release from human airway smooth muscle cells by IL‐1β and TNFα: effects of IL‐10 and corticosteroids

Cited by 96 publications

References 29 publications

Hierarchy of eosinophil chemoattractants: role of p38 mitogen‐activated protein kinase

Hierarchy of eosinophil chemoattractants: role of p38 mitogen‐activated protein kinase

Fractalkine/CX₃CL1 production by human airway smooth muscle cells: induction by IFN-γ and TNF-α and regulation by TGF-β and corticosteroids

Airway smooth muscle cells: contributing to and regulating airway mucosal inflammation?

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Induction of eotaxin expression and release from human airway smooth muscle cells by IL‐1β and TNFα: effects of IL‐10 and corticosteroids

Cited by 96 publications

References 29 publications

Hierarchy of eosinophil chemoattractants: role of p38 mitogen‐activated protein kinase

Hierarchy of eosinophil chemoattractants: role of p38 mitogen‐activated protein kinase

Fractalkine/CX3CL1 production by human airway smooth muscle cells: induction by IFN-γ and TNF-α and regulation by TGF-β and corticosteroids

Airway smooth muscle cells: contributing to and regulating airway mucosal inflammation?

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Fractalkine/CX₃CL1 production by human airway smooth muscle cells: induction by IFN-γ and TNF-α and regulation by TGF-β and corticosteroids