Cell Biochemistry and Biophysics

, Volume 43, Issue 1, pp 119–129

Proinflammatory cytokines upregulate mRNA expression and secretion of vascular endothelial growth factor in cultured human airway smooth muscle cells

  • V. K. T. Alagappan
  • S. McKay
  • A. Widyastuti
  • I. M. Garrelds
  • A. J. J. C. Bogers
  • H. C. Hoogsteden
  • S. J. Hirst
  • H. S. Sharma
Original Article

DOI: 10.1385/CBB:43:1:119

Cite this article as:
Alagappan, V.K.T., McKay, S., Widyastuti, A. et al. Cell Biochem Biophys (2005) 43: 119. doi:10.1385/CBB:43:1:119
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Abstract

Airflow obstruction in chronic airway disease is associated with airway and pulmonary vascular remodeling, of which the molecular mechanisms are poorly understood. Paracrine actions of angiogenic factors released by resident or infiltrating inflammatory cells following activation by proinflammatory cytokines in diseased airways could play a major role in the airway vascular remodeling process. Here, the proinflammatory cytokines interleukin (IL)-1β, and tumor necrosis factor (TNF)-α were investigated on cell cultures of human airway smooth muscle (ASM) for their effects on mRNA induction and protein release of the angiogenic peptide, vascular endothelial growth factor (VEGF). IL-1β (0.5 ng/mL) and TNF-α (10ng/mL) each increased VEGF mRNA (3.9 and 1.7 kb) expression in human ASM cells, reaching maximal levels between 16 and 24 and 4 and 8h, respectively. Both cytokines also induced a time-dependent release of VEGF, which was not associated with increased ASM growth. Preincubation of cells with 1μM dexamethasone abolished enhanced release of VEGF by TNF-α. The data suggest that human ASM cells express and secrete VEGF in response to proinflammatory cytokines and may participate in paracrine inflammatory mechanisms of vascular remodeling in chronic airway disease.

Index Entries

Cytokinevascular endothelial growth factorairway smooth muscleenzymelinked immunosorbent assayhuman

Copyright information

© Humana Press Inc 2005

Authors and Affiliations

  • V. K. T. Alagappan
    • 1
  • S. McKay
    • 1
  • A. Widyastuti
    • 1
  • I. M. Garrelds
    • 1
  • A. J. J. C. Bogers
    • 2
  • H. C. Hoogsteden
    • 3
  • S. J. Hirst
    • 4
  • H. S. Sharma
    • 1
  1. 1.Department of PharmacologyUniversity Medical Center RotterdamRotterdamThe Netherland
  2. 2.Department of Cardiothoracic SurgeryUniversity Medical Center RotterdamRotterdamThe Netherland
  3. 3.Department of Pulmonary Medicine Erasmus MCUniversity Medical Center RotterdamRotterdamThe Netherland
  4. 4.Asthma, Allergy & Respiratory Science, The Guy's, King's College & St. Thomas' School of MedicineKing's College LondonLondonUK