Oncostatin M causes eotaxin-1 release from airway smooth muscle: Synergy with IL-4 and IL-13
Oncostatin M causes eotaxin-1 release from airway smooth muscle: Synergy with IL-4 and IL-13
复制标题
DOI：
10.1016/j.jaci.2004.11.033
复制
发表时间：
2005-03-01
影响因子：
14.2
通讯作者：
Shore, SA
中科院分区：
文献类型：
--
作者：
Faffe, DS;Flynt, L;Shore, SA
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-4R alpha, 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 I 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-4R alpha 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 11-4 to increase eotaxin I expression, possibly as a result of effects on IL-4Ra expression.
