TGF-beta differentially regulates TH2 cytokine-induced eotaxin and eotaxin-3 release by human airway smooth muscle cells.
BACKGROUND
Human airway smooth muscle cells (HASMs) are involved in the pathogenesis of asthma. By producing chemokines, HASMs play a role in the inflammatory processes observed in this disease. Eotaxin, eotaxin-2, and eotaxin-3 are important chemoattractants for eosinophils, and these chemokines are expressed during different phases of the allergic reaction. TH2 cytokines and TGF-beta can be found in increased levels in patients with asthma, and these cytokines may be involved in the regulation of chemokine expression.


OBJECTIVE
The aim of this study was to determine the effect of TH2 cytokines and TGF-beta on the regulation of expression of eotaxin, eotaxin-2, and eotaxin-3 by HASMs.


METHODS
HASMs were incubated for 24 hours with IL-4, IL-13, TGF-beta1, or combinations of these cytokines. Protein and mRNA levels of eotaxin and eotaxin-3 were evaluated by sandwich ELISA and reverse transcriptase-PCR.


RESULTS
IL-4 and IL-13 induced mRNA and protein for both eotaxin and eotaxin-3. Eotaxin-2 mRNA and protein were not detected in HASMs. TGF-beta alone did not induce expression of the eotaxins. However, in combination with IL-4 or IL-13, TGF-beta enhanced eotaxin production and inhibited TH2 cytokine-induced eotaxin-3 production.


CONCLUSIONS
TGF-beta differentially regulates TH2 cytokine-induced eotaxin and eotaxin-3 release.
Department of Pulmonology, Leiden University Medical Center, The Netherlands. s.zuyderduyn@lumc.nl
Suzanne
S
Zuyderduyn
Pieter S
PS
Hiemstra
Klaus F
KF
Rabe
D001980:Bronchi / Q000276:immunology; D054413:Chemokine CCL11; D000075906:Chemokine CCL26; D019742:Chemokines, CC / Q000276:immunology*; D006801:Humans; D018793:Interleukin-13 / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D032389:Myocytes, Smooth Muscle / Q000276:immunology*; D011014:Pneumonia / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000276:immunology*
C515456:CCL11 protein, human; C120429:CCL26 protein, human; D054413:Chemokine CCL11; D000075906:Chemokine CCL26; D019742:Chemokines, CC; D018793:Interleukin-13; D016212:Transforming Growth Factor beta; D015847:Interleukin-4