Regulation of human eotaxin-3/CCL26 expression: modulation by cytokines and glucocorticoids.
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)-alpha or interleukin (IL)-1 beta alone. Both IL-4 and IL-13 acted synergistically with TNF-alpha 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 Th(2) cytokines is different from that of Eotaxin-1 and Eotaxin-2, further supporting a distinct biological role for Eotaxin-3.
Banwell
Miles Edwin
ME
Leukocyte Biology Section, Biomedical Sciences Division, Imperial College School of Medicine, South Kensington, London SW7 2AZ, UK. m.banwell@ic.ac.uk
Tolley
Neil Samuel
NS
Williams
Timothy John
TJ
Mitchell
Tracey Jane
TJ
D002460:Cell Line; D054413:Chemokine CCL11; D054423:Chemokine CCL24; D000075906:Chemokine CCL26; D019742:Chemokines, CC / Q000235:genetics*; D016207:Cytokines / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology*; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D018793:Interleukin-13 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D007700:Kinetics; D008168:Lung / Q000502:physiology*; D020545:Respiratory Mucosa / Q000502:physiology*; D014158:Transcription, Genetic / Q000187:drug effects
C515456:CCL11 protein, human; C515484:CCL24 protein, human; C120429:CCL26 protein, human; D054413:Chemokine CCL11; D054423:Chemokine CCL24; D000075906:Chemokine CCL26; D019742:Chemokines, CC; D016207:Cytokines; D005938:Glucocorticoids; D018793:Interleukin-13; D015847:Interleukin-4; D003907:Dexamethasone