Expression of the chemokine RANTES by a human bronchial epithelial cell line. Modulation by cytokines and glucocorticoids.
The chemokine RANTES is a potent chemoattractant for eosinophils, lymphocytes, and monocytes, and has been detected recently in the epithelium of human airways mucosa. We have studied, therefore, the expression of RANTES mRNA and protein in the human bronchial epithelial cell line BEAS-2B. Using Northern blot analysis, RANTES mRNA was not detectable in unstimulated BEAS-2B cells. Incubation of cells with TNF-alpha or IFN-gamma induced the expression of RANTES mRNA and protein within 16 h. The combination of TNF-alpha and IFN-gamma displayed a marked synergism in inducing RANTES expression. Pretreatment of cells with the glucocorticoid budesonide (10(-10)-10(-7) M) for 24 h inhibited expression of RANTES mRNA and protein stimulated by either TNF-alpha or TNF-alpha plus IFN-gamma in a concentration- and time-dependent manner. Nonglucocorticoid steroids did not inhibit RANTES mRNA expression. Production of RANTES by epithelium could contribute to the mechanism of selective cellular recruitment occurring in the airways during inflammation, thus playing a relevant role in the pathogenesis of diseases such as asthma, rhinitis, and polyposis. The down-regulation of RANTES production by glucocorticoids in epithelial cells may contribute to the efficacy of these compounds in reducing cellular infiltration and, ultimately, to their anti-inflammatory properties.
Stellato
C
C
Johns Hopkins Asthma and Allergy Center, Baltimore, MD 21224, USA.
Beck
L A
LA
Gorgone
G A
GA
Proud
D
D
Schall
T J
TJ
Ono
S J
SJ
Lichtenstein
L M
LM
Schleimer
R P
RP
D015152:Blotting, Northern; D001980:Bronchi / Q000187:drug effects* / Q000378:metabolism*; D001993:Bronchodilator Agents / Q000494:pharmacology; D019819:Budesonide; D002460:Cell Line; D018946:Chemokine CCL5; D016207:Cytokines / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000502:physiology; D015847:Interleukin-4 / Q000502:physiology; D008222:Lymphokines / Q000235:genetics*; D011282:Pregnenediones / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D001993:Bronchodilator Agents; D018946:Chemokine CCL5; D016207:Cytokines; D008222:Lymphokines; D011282:Pregnenediones; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D019819:Budesonide; D007371:Interferon-gamma