TY - JOUR
T1 - Human Airway Smooth Muscle Cells Express and Release RANTES in Response to T Helper 1 Cytokines
T2 - Regulation by T Helper 2 Cytokines and Corticosteroids
AU - John, Matthias
AU - Hirst, Stuart J.
AU - Jose, Peter J.
AU - Robichaud, Annette
AU - Berkman, Neville
AU - Witt, Christian
AU - Twort, Charles H.C.
AU - Barnes, Peter J.
AU - Chung, K. Fan
PY - 1997/2/15
Y1 - 1997/2/15
N2 - RANTES is a basic 8-kDa polypeptide of the C-C chemokine subfamily with strong chemotactic activity for eosinophils, lymphocytes, and monocytes. We determined the regulation of RANTES production by human airway smooth muscle cells in culture. While TNF-α, but not IFN-γ, increased RANTES mRNA expression and protein release, the combination of TNF-α and IFN-γ caused a greater degree of expression and release in a time- and dose-dependent manner. Sequential treatment of airway smooth muscle cells with TNF-α and IFN-γ showed that IFN-γ sensitized the cells to the stimulatory effect of TNF-α. Using a modified Boyden chamber technique, RANTES separated by reverse-phase liquid chromatography from cell culture supernatants of airway smooth muscle cells stimulated by TNF-α and IFN-γ showed a strong chemoattractant effect on human eosinophils, an effect inhibited by an anti-RANTES Ab. RANTES production induced by TNF-α and IFN-γ was inhibited partly by the Th2-derived cytokines, IL-4, IL-10, and IL-13, as well as by dexamethasone. Our studies indicate that, in addition to contractile responses and mitogenesis, airway smooth muscle cells have synthetic and secretory potential with the release of RANTES. They may participate in chronic airway inflammation by interacting with both Th1- and Th2-derived cytokines to modulate chemoattractant activity for eosinophils, activated T lymphocytes, and monocytes/macrophages.
AB - RANTES is a basic 8-kDa polypeptide of the C-C chemokine subfamily with strong chemotactic activity for eosinophils, lymphocytes, and monocytes. We determined the regulation of RANTES production by human airway smooth muscle cells in culture. While TNF-α, but not IFN-γ, increased RANTES mRNA expression and protein release, the combination of TNF-α and IFN-γ caused a greater degree of expression and release in a time- and dose-dependent manner. Sequential treatment of airway smooth muscle cells with TNF-α and IFN-γ showed that IFN-γ sensitized the cells to the stimulatory effect of TNF-α. Using a modified Boyden chamber technique, RANTES separated by reverse-phase liquid chromatography from cell culture supernatants of airway smooth muscle cells stimulated by TNF-α and IFN-γ showed a strong chemoattractant effect on human eosinophils, an effect inhibited by an anti-RANTES Ab. RANTES production induced by TNF-α and IFN-γ was inhibited partly by the Th2-derived cytokines, IL-4, IL-10, and IL-13, as well as by dexamethasone. Our studies indicate that, in addition to contractile responses and mitogenesis, airway smooth muscle cells have synthetic and secretory potential with the release of RANTES. They may participate in chronic airway inflammation by interacting with both Th1- and Th2-derived cytokines to modulate chemoattractant activity for eosinophils, activated T lymphocytes, and monocytes/macrophages.
UR - http://www.scopus.com/inward/record.url?scp=0031568394&partnerID=8YFLogxK
M3 - Article
C2 - 9029124
AN - SCOPUS:0031568394
SN - 0022-1767
VL - 158
SP - 1841
EP - 1847
JO - Journal of Immunology
JF - Journal of Immunology
IS - 4
ER -