Expression and release of interleukin-8 by human airway smooth muscle cells: inhibition by Th-2 cytokines and corticosteroids.
Interleukin (IL)-8 is a C-X-C chemokine that potently chemoattracts and activates neutrophils. We determined whether IL-8 could be produced by human airway smooth muscle cells in culture and examined its regulation. TNF-alpha stimulated IL-8 mRNA expression and protein release in a time- and dose-dependent manner, whereas IFN-gamma alone had no effect. Both cytokines together did not induce greater IL-8 release compared to TNF-alpha alone. IL-1beta was more potent in inducing IL-8 release and, together with TNF-alpha, there was a synergistic augmentation of IL-8 release. IL-8 release induced by TNF-alpha and IFN-gamma was partly inhibited by the Th-2-derived cytokines IL-4, IL-10, and IL-13, as well as by dexamethasone. In addition to its contractile responses, airway smooth muscle cells have synthetic and secretory potential with the release of IL-8 and subsequent recruitment and activation of neutrophils in the airways. Release of IL-8 can be modulated by Th-2-derived cytokines and corticosteroids.
John
M
M
Thoracic Medicine and Applied Pharmacology, National Heart and Lung Institute, Imperial College School of Medicine, London, United Kingdom.
Au
B T
BT
Jose
P J
PJ
Lim
S
S
Saunders
M
M
Barnes
P J
PJ
Mitchell
J A
JA
Belvisi
M G
MG
Chung
K F
KF
D000305:Adrenal Cortex Hormones / Q000494:pharmacology*; D001980:Bronchi / Q000378:metabolism*; D001984:Bronchial Neoplasms; D016207:Cytokines / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D016753:Interleukin-10 / Q000494:pharmacology; D018793:Interleukin-13 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D016209:Interleukin-8 / Q000235:genetics* / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D009130:Muscle, Smooth / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000305:Adrenal Cortex Hormones; D016207:Cytokines; D007375:Interleukin-1; D018793:Interleukin-13; D016209:Interleukin-8; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma