دورية أكاديمية
TH2 Cytokines and Allergic Challenge Induce Ym1 Expression in Macrophages by a STAT6-dependent Mechanism
| العنوان: | TH2 Cytokines and Allergic Challenge Induce Ym1 Expression in Macrophages by a STAT6-dependent Mechanism |
|---|---|
| المؤلفون: | Welch, John Crawford, Escoubet-Lozach, Laure, Sykes, David Brian, Liddiard, Kate, Greaves, David R., Glass, Christopher K. |
| بيانات النشر: | American Society for Biochemistry & Molecular Biology (ASBMB) |
| سنة النشر: | 2002 |
| المجموعة: | Harvard University: DASH - Digital Access to Scholarship at Harvard |
| الوصف: | The diverse functions of macrophages as participants in innate and acquired immune responses are regulated by the specific milieu of environmental factors, cytokines, and other signaling molecules that are encountered at sites of inflammation. Microarray analysis of the transcriptional response of mouse peritoneal macrophages to the TH2 cytokine interleukin-4 (IL-4) identified Ym1 and arginase as the most highly up-regulated genes, exhibiting more than 68- and 88-fold induction, respectively. Molecular characterization of the Ym1 promoter in transfected epithelial and macrophage cell lines revealed the presence of multiple signal transducers and activators of transcription 6 (STAT6) response elements that function in a combinatorial manner to mediate transcriptional responses to IL-4. The participation of STAT6 as an obligate component of protein complexes binding to these sites was established by analysis of nuclear extracts derived from STAT6-deficient macrophages. Macrophage expression of Ym1 was highly induced in vivo by an IL-4- and STAT6-dependent mechanism during the evolution of allergic peritonitis, supporting the biological relevance of the IL-4-dependent pathway characterized ex vivo in peritoneal macrophages. These studies establish Ym1 as a highly inducible STAT6-dependent transcript in TH2-biased inflammation and define Cis-active elements in the Ym1 promoter that are required for this transcriptional response. The macrophage plays an important role bridging between innate and acquired immune function. It is capable both of responding to nonspecific stimuli, such as bacterial lipopolysaccarides (LPS)1 and activated complement factors, but can also engage processes of the acquired immune response such as antibody-dependent opsonization and subsequent antigen presentation to T-cells (1, 2). Macrophage function can be influenced profoundly by cytokines released from T-cells and other immune cells. These cytokines have been divided largely along two axes: TH1 cytokines, dominated by INF-γ and TH2 ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 0021-9258 |
| العلاقة: | Journal of Biological Chemistry; Quick submit: 2017-06-09T12:37:41-0400; Welch, John S., Laure Escoubet-Lozach, David B. Sykes, Kate Liddiard, David R. Greaves, and Christopher K. Glass. 2002. “TH2 Cytokines and Allergic Challenge Induce Ym1 Expression in Macrophages by a STAT6-Dependent Mechanism.” Journal of Biological Chemistry 277 (45) (September 4): 42821–42829. doi:10.1074/jbc.m205873200.; http://nrs.harvard.edu/urn-3:HUL.InstRepos:37137073Test |
| DOI: | 10.1074/jbc.M205873200 |
| الإتاحة: | https://doi.org/10.1074/jbc.M205873200Test https://doi.org/10.1074/jbc.m205873200Test http://nrs.harvard.edu/urn-3:HUL.InstRepos:37137073Test |
| رقم الانضمام: | edsbas.1B4011B5 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 00219258 |
|---|---|
| DOI: | 10.1074/jbc.M205873200 |