Journal article
Negative role of cAMP‐dependent protein kinase A in RANTES‐mediated transcription of proinflammatory mediators through Raf
The FASEB journal, Vol.17(6), pp.734-736
04/2003
DOI: 10.1096/fj.02-0962fje
PMID: 12586731
Abstract
ABSTRACT
The chemokine RANTES (regulated on activation normal T cell expressed and secreted) is expressed in several inflammatory diseases of the central nervous system and is a powerful stimulus for astrocyte production of proinflammatory mediators. The mechanism of RANTES‐mediated astrocyte activation was investigated. RANTES stimulation decreased both intracellular cyclic AMP (cAMP) levels and cAMP‐dependent protein kinase A (PKA) activity in cultures of primary mouse astrocytes. H‐89, a potent inhibitor of PKA, mimicked RANTES‐mediated chemokine and cytokine transcription. RANTES treatments activated Raf‐1 kinase activity, and conversely a dominant negative Raf and a Raf‐1 inhibitor blocked RANTES‐induced chemokine transcription. Transfection with a constitutively active Raf was sufficient to induce transcription of proinflammatory mediators. The combined data indicate that Raf‐1 is required for RANTES‐mediated astrocyte activation. Decreases of cAMP and PKA activity contributed to the transcription of proinflammatory mediators by cross‐talk with the Raf‐1/mitogen‐activated protein kinase pathway. The results identify an upstream signaling pathway for amplification of proinflammatory mediators in the central nervous system.
Details
- Title: Subtitle
- Negative role of cAMP‐dependent protein kinase A in RANTES‐mediated transcription of proinflammatory mediators through Raf
- Creators
- Ye Zhang - Harvard UniversityYi Luo - Harvard Medical SchoolQiwei Zhai - Department of NeurologyChildren's HospitalBostonMA02115Liying Ma - Harvard Medical SchoolMartin E. Dorf - Harvard Medical School
- Resource Type
- Journal article
- Publication Details
- The FASEB journal, Vol.17(6), pp.734-736
- Publisher
- Federation of American Societies for Experimental Biology
- DOI
- 10.1096/fj.02-0962fje
- PMID
- 12586731
- ISSN
- 0892-6638
- eISSN
- 1530-6860
- Number of pages
- 20
- Grant note
- National Multiple Sclerosis Society (RG2989B3) Hoechst Marion Roussel Collaboration National Institutes of Health (NS37284; CA67416)
- Language
- English
- Date published
- 04/2003
- Academic Unit
- Urology
- Record Identifier
- 9984320073602771
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