Cardiac fibroblasts arrest at the G1/S restriction point in response to interleukin (IL)-1β: Evidence for IL-1β-induced hypophosphorylation of the retinoblastoma protein

Farid Koudssi, Javier E Lopez, Sonia Villegas, Carlin S. Long

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Although responsible for only approximately one-third of the overall myocardial mass, the interstitial fibroblasts of the heart serve a fundamental role in establishing the functional integrity of myocardium and are the major source of myocardial extracellular matrix production. Their importance in clinical medicine is underscored by the observation that fibroblast numbers increase in response to several pathologic circumstances that are associated with an increase in extracellular matrix production, such as long standing hypertension and myocardial injury/infarction. Up to the present time, however, there has been little information available on either the kinetics of the cardiac fibroblast cell cycle, or the fundamental mechanisms that regulate its entry into and exit from the cell cycle. Previous work from our laboratory examining the effects of interleukin (IL)- 1β on myocardial growth and gene expression in culture indicated that cardiac fibroblasts have a diminished capacity to synthesize DNA in response to mitogen in the presence of this cytokine. The mechanism of IL-1β action was not clear, however, and could have resulted from action at several different points in the cell cycle. The investigations described in this report indicate that IL-1β exerts its effect on the fibroblast cell cycle at multiple levels through altering the expression of cardiac fibroblast cyclins, cyclin-dependent kinases, and their inhibitors, which ultimately affect the phosphorylation of the retinoblastoma gene product.

Original languageEnglish (US)
Pages (from-to)25796-25803
Number of pages8
JournalJournal of Biological Chemistry
Volume273
Issue number40
DOIs
StatePublished - Oct 2 1998
Externally publishedYes

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G1 Phase Cell Cycle Checkpoints
Retinoblastoma Protein
Fibroblasts
Heart Arrest
Interleukin-1
Cell Cycle
Cells
Extracellular Matrix
Retinoblastoma Genes
Phosphorylation
Cyclins
Cyclin-Dependent Kinases
Clinical Medicine
Mitogens
Cell culture
Gene expression
Medicine
Myocardium
Genes
Myocardial Infarction

ASJC Scopus subject areas

  • Biochemistry

Cite this

Cardiac fibroblasts arrest at the G1/S restriction point in response to interleukin (IL)-1β : Evidence for IL-1β-induced hypophosphorylation of the retinoblastoma protein. / Koudssi, Farid; Lopez, Javier E; Villegas, Sonia; Long, Carlin S.

In: Journal of Biological Chemistry, Vol. 273, No. 40, 02.10.1998, p. 25796-25803.

Research output: Contribution to journalArticle

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