Induction of eotaxin expression and release from human airway smooth muscle cells by IL-1beta and TNFalpha: effects of IL-10 and corticosteroids.
Eotaxin is a novel C-C chemokine with selective chemoattractant activity for eosinophils. We determined whether eotaxin could be produced by human airway smooth muscle (HASM) cells in culture and examined its regulation by interleukin-10 (IL-10) and the corticosteroid, dexamethasone. Stimulation of the cells with interleukin-1beta (IL-1beta) or tumour necrosis factor (TNFalpha) each at 10 ng ml(-1) induced the release of eotaxin protein with maximal accumulation by 24 h. Interferon-gamma (IFNgamma) alone at 10 ng ml(-1) had no effect and there was no synergy between these cytokines on the release of eotaxin. Reverse phase high performance liquid chromatographic (HPLC) analysis of supernatents from cells treated with TNFalpha (10 ng ml(-1) for 96 h showed immunoreactivity to eotaxin which eluted with the expected retention time of 34.5-35 min. Both IL-1beta and TNFalpha-induced release of eotaxin was not inhibited by dexamethasone (1 microM), however IL-10 (10 ng ml(-1)) had a significant inhibitory effect. Dexamethasone and IL-10 did not inhibit the induction of eotaxin mRNA induced by IL-1beta or TNFalpha. Thus, human airway smooth muscle cells can release eotaxin and could be an important source of chemokine production during airway inflammatory events.
Chung
K F
KF
Thoracic Medicine, National Heart and Lung Institute, London. f.chung@ic.ac.uk
Patel
H J
HJ
Fadlon
E J
EJ
Rousell
J
J
Haddad
E B
EB
Jose
P J
PJ
Mitchell
J
J
Belvisi
M
M
D000293:Adolescent; D000328:Adult; D001980:Bronchi / Q000378:metabolism*; D002478:Cells, Cultured; D054413:Chemokine CCL11; D018946:Chemokine CCL5 / Q000096:biosynthesis; D019742:Chemokines, CC; D002648:Child; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology*; D016753:Interleukin-10 / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009130:Muscle, Smooth / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D014132:Trachea / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
C515456:CCL11 protein, human; D054413:Chemokine CCL11; D018946:Chemokine CCL5; D019742:Chemokines, CC; D016207:Cytokines; D007375:Interleukin-1; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D003907:Dexamethasone; D007371:Interferon-gamma