IL-1 beta stimulates rat cardiac fibroblast migration via MAP kinase pathways

Mitchell, M.D., Laird, R.E., Brown, R.D. and Long, C.S. (2007) IL-1 beta stimulates rat cardiac fibroblast migration via MAP kinase pathways. American Journal of Physiology-heart And Circulatory Physiology, 292 2: H1139-H1147. doi:10.1152/ajpheart.00881.2005

Author Mitchell, M.D.
Laird, R.E.
Brown, R.D.
Long, C.S.
Title IL-1 beta stimulates rat cardiac fibroblast migration via MAP kinase pathways
Journal name American Journal of Physiology-heart And Circulatory Physiology   Check publisher's open access policy
ISSN 0002-9513
Publication date 2007-02
Sub-type Article (original research)
DOI 10.1152/ajpheart.00881.2005
Volume 292
Issue 2
Start page H1139
End page H1147
Total pages 9
Place of publication Washington, DC, U.S.A.
Publisher American Physiological Society
Language eng
Subject 1102 Cardiovascular Medicine and Haematology
1103 Clinical Sciences
Formatted abstract
The pro-inflammatory cytokines interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) are elevated following acute myocardial infarction (MI) and have been implicated in the pathophysiology of cardiac disease progression. The cardiac fibroblast represents an important effector cell target for cytokine actions. In particular, cytokine-directed cardiac fibroblast migration is likely to impact both myocardial repair following acute MI and pathological myocardial remodeling in the progression to heart failure. In the present study, we examined the migratory response of neonatal rat cardiac fibroblasts to pro-inflammatory cytokines using modified Boyden chamber assays. On the basis of the knowledge of migration in other cell types, we hypothesized that members of the mitogen-activated protein kinase (MAPK) family may regulate this process. This possibility was addressed with the use of immunoblot detection of active phosphorylated MAPK species and pharmacological inhibitors for individual members of the MAPK cascades. IL-1β stimulated robust and concentration-dependent increases in migration (maximum, 20-fold over control cells). TNF-α had lesser effect (fourfold increase over control). IL-6 did not induce migration. Activation of all three MAPK subfamilies (extracellular signal-regulated kinases, c-Jun NH2-terminal kinases, and p38) was shown to occur in response to cytokine stimulation. Fibroblast migration was attenuated by pharmacological inhibition of each MAPK subfamily. Understanding the regulation of cardiac fibroblast migration may provide insights in the search for therapies aimed at enhancing the functional nature of the remodeling process. Copyright © 2007 the American Physiological Society.
Keyword Interleukin-1
Tumor necrosis factor-alpha
Myocardial remodeling
Mitogen-activated protein kinases
Activated Protein-kinase
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collection: UQ Centre for Clinical Research Publications
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Created: Thu, 26 Aug 2010, 13:05:13 EST