REGULATION OF HUMAN EOTAXIN-3/CCL26 EXPRESSION: MODULATION BY CYTOKINES AND GLUCOCORTICOIDS

doi:10.1006/cyto.2002.1021

Cytokine

Volume 17, Issue 6, March 2002, Pages 317-323

https://doi.org/10.1006/cyto.2002.1021 Get rights and content

Abstract

Eotaxin-3 (CCL26) is a CC chemokine that signals exclusively via the CCR3 receptor and has eosinophil-selective chemoattractant activity. Comparison of Eotaxin-1 (CCL11) and Eotaxin-2 (CCL24), demonstrates differences in their expression profiles, cell specificity and effector kinetics, implying distinct biological actions. But little data in this regard have been reported for Eotaxin-3. We aimed to analyse the effect of Th2 cytokines and glucocorticoids on Eotaxin-3 mRNA expression in human lung epithelial cells and dermal fibroblasts; cells implicated in the pathogenesis of allergic asthma and allergic dermatitis respectively. Eotaxin-3 mRNA levels in primary dermal fibroblasts and NCI-H727 lung epithelial cells were determined by Northern hybridization. In contrast to Eotaxin-1, Eotaxin-3 mRNA expression was not detected in unstimulated cells. The Th2 cytokines IL-4 and IL-13 induced Eotaxin-3 expression in a time and dose dependent manner, with IL-4 demonstrating a 100-fold greater potency. Unlike Eotaxin-1, Eotaxin-3 mRNA expression was not induced by either tumour necrosis factor (TNF)-α or interleukin (IL)-1β alone. Both IL-4 and IL-13 acted synergistically with TNF-α in superinducing Eotaxin-3 mRNA expression. Dexamethasone pre-treatment diminished induction of Eotaxin-3 mRNA expression. We conclude that modulation of Eotaxin-3 mRNA expression by Th₂ cytokines is different from that of Eotaxin-1 and Eotaxin-2, further supporting a distinct biological role for Eotaxin-3.

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CCL26 is a chemokine that belongs to the eotaxin family (eotaxin-1/CCL11, eotaxin-2/CCL24, and eotaxin-3/CCL26) [114]. Eotaxins are released by epithelial, mesenchymal, and endothelial cells in response to various mediators, including IL-4, IL-13, and TNF-α [115–117]. Eotaxins are potent chemoattractants for eosinophils [115,117], which play a central role in type-2 immunity such as host defense against parasitic helminth infections, tissue repair and remodeling, and allergic diseases [118,119].
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1) In the overall study population, vaginal concentrations of CXCL10, CCL2, CCL3, SLP1 and VEGF negatively correlated with non-Lactobacillus, Community State Type IV (CST IV) members of the vaginal microbiome; 2) CXCL10, in particular, negatively correlated with 15 bacterial phylotypes, most of which are typical members of CST IV, such as Gardnerella vaginalis, Megasphaera spp., and Atopobium vaginae; 3) Gemella spp., also members of CST IV, negatively correlated with vaginal concentrations of VEGF, CCL2, CCL3, SLPI, and CXCL10; 4) when comparing PTB cases to term controls, five soluble immune mediators (CCL26, CCL22, CCL2, CXCL10, and IL-16), especially CCL26, were negatively correlated with five typical members of CST IV: Sneathia sanguinegens, Parvimonas micra, Veillonellaceae, BVAB2, and Gemella spp.; and 5) Sneathia sanguinegens had stronger negative associations with all five soluble immune mediators (CCL26, CCL22, CCL2, CXCL10, and IL-16) in PTB cases than in term controls.
The assessment of vaginal host immune-microbiome interactions revealed that specific soluble immune mediators, mainly CXCL10, negatively correlated with typical members of CST IV of the vaginal microbiome. Sneathia sanguinegens, in particular, had stronger negative associations with different immune mediators, including CXCL10 and CCL26, in women who ultimately underwent PTB compared to those who delivered at term. These findings provide insight into the vaginal host immune-microbiome interactions in normal and complicated pregnancies.
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Eotaxin-1 is secreted by eosinophils, macrophages, lymphocytes, fibroblasts, smooth muscle and endothelial cells, whereas eotaxin-2 and eotaxin-3 are mainly released by epithelial and endothelial cells [10]. Among these cell types, epithelial cells are the major source of eotaxins and principally release high levels of eotaxin-3 [11–13]. Puerarin, a naturally occurring isoflavonoid, is abundant in the root of the plant Pueraria lobata.
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^f1: Correspondence to: Miles Banwell, Leukocyte Biology Section, Biomedical Sciences Division, Imperial College School of Medicine, South Kensington, London SW7 2AZ, UK. E-mail: [email protected]

^f2: Present address: T. J. Mitchell's, Skin Tumour Unit, St. Johns Institute of Dermatology, St. Thomas' Hospital, Lambeth Palace Road, London SE1 7EH, UK

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Regular ArticlesREGULATION OF HUMAN EOTAXIN-3/CCL26 EXPRESSION: MODULATION BY CYTOKINES AND GLUCOCORTICOIDS

Abstract

Biochem Biophys Res Commun

J Biol Chem

J Allergy Clin Immunol

J Invest Dermatol

J Invest Dermatol

Eosinophilia

N Engl J Med

Eotaxin: a potent eosinophil chemoattractant cytokine detected in a guinea pig model of allergic airways inflammation

J Exp Med

Cloning of the human eosinophil chemoattractant eotaxin: expression, receptor binding, and functional properties suggest a mechanism for the selective recruitment of eosinophils

J Clin Invest

Eotaxin-2, a novel CC chemokine that is selective for the chemokine receptor CCR3, and acts like eotaxin on human eosinophil and basophil leukocytes

J Exp Med

A novel human CC chemokine, eotaxin-3, which is expressed in IL-4-stimulated vascular endothelial cells, exhibits potent activity toward eosinophils

J Immunol

Human eotaxin is a specific chemoattractant for eosinophil cells and provides a new mechanism to explain tissue eosinophilia

Nat Med

Molecular cloning and characterization of a human eotaxin receptor expressed selectively on eosinophils

J Exp Med

Selective expression of the eotaxin receptor CCR3 by human T helper 2 cells

Science

Regular Articles
REGULATION OF HUMAN EOTAXIN-3/CCL26 EXPRESSION: MODULATION BY CYTOKINES AND GLUCOCORTICOIDS