Heat shock-mediated regulation of MKP-1
In: American journal of physiology. Cell physiology, Jg. 58 (2005), Heft 5, S. C1152- (7S.)
Online
academicJournal
- print, 36 ref
Zugriff:
Heat shock modulates cellular proinflammatory responses, and we have been interested in elucidating the mechanisms that govern this modulation. The dual specific phosphatase, MAP kinase phosphatase-1 (MKP-1), is an important modulator of cellular inflammatory responses, and we recently reported that heat shock increases expression of MKP-1. Herein we sought to elucidate the mechanisms by which heat shock modulates MKP-1 gene expression. Subjecting RAW264.7 macrophages to heat shock increased MKP-1 gene expression in a time-dependent manner. Transfection with a wild-type murine MKP-1 promoter luciferase reporter plasmid demonstrated that heat shock activates the MKP-1 promoter. When the reporter plasmid was transfected into heat shock factor-1 (HSF-1)-null fibroblasts, the MKP-1 promoter was activated in response to heat shock in a manner similar to that of wild-type fibroblasts with intact HSF-1. Site-directed mutagenesis of two potential heat shock elements in the MKP-I promoter demonstrated that both sites are required for basal promoter activity. mRNA stability assays demonstrated that heat shock increased MKP-1 mRNA stability compared with cells maintained at 37°C. Inhibition of p38 MAP kinase activity inhibited heat shock-mediated expression of MKP-1. These data demonstrate that heat shock regulates MKP-1 gene expression at both the transcriptional and posttranscriptional levels. Transcriptional mechanisms are HSF-1 independent but are dependent on putative heat shock elements in the MKP-1 promoter. Posttranscriptional mechanisms involve increased stability of MKP-i mRNA that is partially dependent on p38 MAP kinase activity. These data demonstrate another potential mechanism by which heat shock can modulate inflammation-related signal transduction.
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Heat shock-mediated regulation of MKP-1
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Autor/in / Beteiligte Person: | WONG, Hector R ; DUNSMORE, Katherine E ; PAGE, Kristen ; SHANLEY, Thomas P |
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Zeitschrift: | American journal of physiology. Cell physiology, Jg. 58 (2005), Heft 5, S. C1152- (7S.) |
Veröffentlichung: | Bethesda, MD: American Physiological Society, 2005 |
Medientyp: | academicJournal |
Umfang: | print, 36 ref |
ISSN: | 0363-6143 (print) |
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