Abstract
Background: Eotaxin is implicated in asthmatic eosinophilia. Oncostatin M (OSM) causes eotaxin release from fibroblasts. Objective: We sought to examine the effects and mechanism of action of OSM and other IL-6 family cytokines on eotaxin release from human airway smooth muscle cells. Methods: Eotaxin 1 release was measured by means of ELISA. Western blotting was used to examine mitogen-activated protein kinase and signal transducer and activator of transcription 3 (STAT-3) phosphorylation. Eotaxin promoter activity was analyzed in cells transfected with wild-type STAT-3, a mutant form of STAT-3 that cannot be phosphorylated, and a constitutively active form of STAT-3. The mRNA and protein expression of IL-4Rα, the signaling receptor for IL-4 and IL-13, was evaluated by means of real-time PCR and flow cytometry, respectively. Results: OSM increased eotaxin 1 release and augmented IL-4- or IL-13-induced eotaxin release, whereas other IL-6 family cytokines did not. OSM caused a greater increase in STAT-3 phosphorylation and STAT-3-mediated gene transcription than other IL-6 family cytokines. OSM increased eotaxin promoter activity and augmented IL-13- and IL-4-induced increases in promoter activity. The constitutively active form of STAT-3 increased eotaxin promoter activity, whereas the mutant form of STAT-3 that cannot be phosphorylated significantly reduced eotaxin promoter activity induced by OSM or IL-4 plus OSM. OSM increased IL-4Rα mRNA and protein levels. Conclusions: OSM induces eotaxin 1 expression in human airway smooth muscle cells by a mechanism involving STAT-3. OSM synergizes with IL-13 and IL-4 to increase eotaxin 1 expression, possibly as a result of effects on IL-4Rα expression.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 514-520 |
| Number of pages | 7 |
| Journal | Journal of Allergy and Clinical Immunology |
| Volume | 115 |
| Issue number | 3 |
| DOIs | |
| State | Published - Mar 2005 |
| Externally published | Yes |
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Keywords
- c-Jun N-terminal kinase
- Extracellular signal-regulated kinase
- IL-4Rα
- Monocyte chemoattractant protein 1
- Signal transducer and activator of transcription 3
- Vascular endothelial growth factor
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
Cite this
Oncostatin M causes eotaxin-1 release from airway smooth muscle : Synergy with IL-4 and IL-13. / Faffe, Débora S.; Flynt, Lesley; Mellema, Matthew; Moore, Paul E.; Silverman, Eric S.; Subramaniam, Venkat; Jones, Matthew R.; Mizgerd, Joseph P.; Whitehead, Timothy; Imrich, Amy; Panettieri, Reynold A.; Shore, Stephanie A.
In: Journal of Allergy and Clinical Immunology, Vol. 115, No. 3, 03.2005, p. 514-520.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Oncostatin M causes eotaxin-1 release from airway smooth muscle
T2 - Synergy with IL-4 and IL-13
AU - Faffe, Débora S.
AU - Flynt, Lesley
AU - Mellema, Matthew
AU - Moore, Paul E.
AU - Silverman, Eric S.
AU - Subramaniam, Venkat
AU - Jones, Matthew R.
AU - Mizgerd, Joseph P.
AU - Whitehead, Timothy
AU - Imrich, Amy
AU - Panettieri, Reynold A.
AU - Shore, Stephanie A.
PY - 2005/3
Y1 - 2005/3
N2 - Background: Eotaxin is implicated in asthmatic eosinophilia. Oncostatin M (OSM) causes eotaxin release from fibroblasts. Objective: We sought to examine the effects and mechanism of action of OSM and other IL-6 family cytokines on eotaxin release from human airway smooth muscle cells. Methods: Eotaxin 1 release was measured by means of ELISA. Western blotting was used to examine mitogen-activated protein kinase and signal transducer and activator of transcription 3 (STAT-3) phosphorylation. Eotaxin promoter activity was analyzed in cells transfected with wild-type STAT-3, a mutant form of STAT-3 that cannot be phosphorylated, and a constitutively active form of STAT-3. The mRNA and protein expression of IL-4Rα, the signaling receptor for IL-4 and IL-13, was evaluated by means of real-time PCR and flow cytometry, respectively. Results: OSM increased eotaxin 1 release and augmented IL-4- or IL-13-induced eotaxin release, whereas other IL-6 family cytokines did not. OSM caused a greater increase in STAT-3 phosphorylation and STAT-3-mediated gene transcription than other IL-6 family cytokines. OSM increased eotaxin promoter activity and augmented IL-13- and IL-4-induced increases in promoter activity. The constitutively active form of STAT-3 increased eotaxin promoter activity, whereas the mutant form of STAT-3 that cannot be phosphorylated significantly reduced eotaxin promoter activity induced by OSM or IL-4 plus OSM. OSM increased IL-4Rα mRNA and protein levels. Conclusions: OSM induces eotaxin 1 expression in human airway smooth muscle cells by a mechanism involving STAT-3. OSM synergizes with IL-13 and IL-4 to increase eotaxin 1 expression, possibly as a result of effects on IL-4Rα expression.
AB - Background: Eotaxin is implicated in asthmatic eosinophilia. Oncostatin M (OSM) causes eotaxin release from fibroblasts. Objective: We sought to examine the effects and mechanism of action of OSM and other IL-6 family cytokines on eotaxin release from human airway smooth muscle cells. Methods: Eotaxin 1 release was measured by means of ELISA. Western blotting was used to examine mitogen-activated protein kinase and signal transducer and activator of transcription 3 (STAT-3) phosphorylation. Eotaxin promoter activity was analyzed in cells transfected with wild-type STAT-3, a mutant form of STAT-3 that cannot be phosphorylated, and a constitutively active form of STAT-3. The mRNA and protein expression of IL-4Rα, the signaling receptor for IL-4 and IL-13, was evaluated by means of real-time PCR and flow cytometry, respectively. Results: OSM increased eotaxin 1 release and augmented IL-4- or IL-13-induced eotaxin release, whereas other IL-6 family cytokines did not. OSM caused a greater increase in STAT-3 phosphorylation and STAT-3-mediated gene transcription than other IL-6 family cytokines. OSM increased eotaxin promoter activity and augmented IL-13- and IL-4-induced increases in promoter activity. The constitutively active form of STAT-3 increased eotaxin promoter activity, whereas the mutant form of STAT-3 that cannot be phosphorylated significantly reduced eotaxin promoter activity induced by OSM or IL-4 plus OSM. OSM increased IL-4Rα mRNA and protein levels. Conclusions: OSM induces eotaxin 1 expression in human airway smooth muscle cells by a mechanism involving STAT-3. OSM synergizes with IL-13 and IL-4 to increase eotaxin 1 expression, possibly as a result of effects on IL-4Rα expression.
KW - c-Jun N-terminal kinase
KW - Extracellular signal-regulated kinase
KW - IL-4Rα
KW - Monocyte chemoattractant protein 1
KW - Signal transducer and activator of transcription 3
KW - Vascular endothelial growth factor
UR - http://www.scopus.com/inward/record.url?scp=20044363972&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=20044363972&partnerID=8YFLogxK
U2 - 10.1016/j.jaci.2004.11.033
DO - 10.1016/j.jaci.2004.11.033
M3 - Article
C2 - 15753898
AN - SCOPUS:20044363972
VL - 115
SP - 514
EP - 520
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
SN - 0091-6749
IS - 3
ER -