Expression of monocyte chemotactic protein (MCP)-1, MCP-2, and MCP-3 by human airway smooth-muscle cells. Modulation by corticosteroids and T-helper 2 cytokines.
We have demonstrated that, in addition to their contractile function, human airway smooth-muscle cells (HASMC) are able to express and to secrete chemokines of the monocyte chemotactic protein (MCP)/ eotaxin subfamily. This group of chemokines is believed to play a fundamental role in the development of allergic airway diseases such as asthma. The expression levels of MCP (MCP-1, -2, and -3) messenger RNA (mRNA) were compared with those of regulated on activation, normal T cells expressed and secreted (RANTES) mRNA in HASMC in culture. HASMC express MCP and RANTES mRNA after stimulation with interleukin (IL)-1beta, tumor necrosis factor-alpha, and interferon-gamma. MCP mRNA was maximal at 8 h, whereas RANTES mRNA expression was delayed to 24 h after stimulation. Further, significant differences were observed in the induction patterns of MCP and RANTES mRNA expression after stimulation with the individual cytokines. Dexamethasone (DEX) significantly inhibited cytokine-induced accumulation of MCP and RANTES mRNA, in contrast to IL-4, IL-10, and IL-13, which had no inhibitory effect on cytokine-induced chemokine expression. The cytokine-induced MCP mRNA expression in HASMC was associated with MCP release, which was inhibited by DEX and post-translationally by IL-4. HASMC can actively participate in the pathogenesis of asthma by the expression and release of chemokines, which are likely to play a critical role in the generation and regulation of the inflammatory response characteristic of allergic airway diseases.
Pype
J L
JL
Laboratory of Pneumology, Laboratory of Molecular Immunology, Rega Institute, Katholieke Universiteit, Leuven, Belgium.
Dupont
L J
LJ
Menten
P
P
Van Coillie
E
E
Opdenakker
G
G
Van Damme
J
J
Chung
K F
KF
Demedts
M G
MG
Verleden
G M
GM
D001980:Bronchi / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics*; D018946:Chemokine CCL5 / Q000235:genetics; D054410:Chemokine CCL7; D054412:Chemokine CCL8; D003513:Cycloheximide / Q000494:pharmacology; D016207:Cytokines / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D016753:Interleukin-10 / Q000494:pharmacology; D018793:Interleukin-13 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D018945:Monocyte Chemoattractant Proteins / Q000235:genetics*; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology
C515450:CCL7 protein, human; C515453:CCL8 protein, human; D018932:Chemokine CCL2; D018946:Chemokine CCL5; D054410:Chemokine CCL7; D054412:Chemokine CCL8; D016207:Cytokines; D005938:Glucocorticoids; D018793:Interleukin-13; D018945:Monocyte Chemoattractant Proteins; D012333:RNA, Messenger; D016753:Interleukin-10; D015847:Interleukin-4; D003907:Dexamethasone; D003513:Cycloheximide