Molecular and Cellular Biochemistry

, Volume 292, Issue 1, pp 169–178

TNF-α, IFN-γ, and IL−1β modulate hyaluronan synthase expression in human skin fibroblasts: Synergistic effect by concomital treatment with FeSO4 plus ascorbate

  • Giuseppe M. Campo
  • Angela Avenoso
  • Salvatore Campo
  • D'Ascola Angela
  • Alida M. Ferlazzo
  • Alberto Calatroni

DOI: 10.1007/s11010-006-9230-7

Cite this article as:
Campo, G.M., Avenoso, A., Campo, S. et al. Mol Cell Biochem (2006) 292: 169. doi:10.1007/s11010-006-9230-7


Several reports have shown that a number of cytokines such as tumor necrosis-α (TNF-α), interferon-γ (IFN-γ), and interleukin-β (IL-1β) are capable to induce hyaluronan sinthases (HASs) mRNA expression in different cell culture types. The obvious consequence of this stimulation is a marked increment in hyaluronan (HA) production. It has been also reported that oxidative stress, by itself, may increase HA levels. The aim of this study was to evaluate how TNF-α, IFN-γ,IL−1β, and exposition to oxidative stress may modulate HAS activities in normal human skin fibroblasts. Moreover, the effects on HAS mRNA expression of the concomitant treatment with cytokines and oxidants, and the HA concentrations after treatments, were studied. TNF-α, IFN-γ, and IL-1β were added to normal or/and exposed to FeSO4 plus ascorbate fibroblast cultures and HAS1, HAS2 and HAS3 mRNA content, by PCR-real time, was assayed 3,h later. HA levels were also evaluated after 24,h incubation. The treatment of fibroblasts with cytokines up-regulated HASs gene expression and increased HA production. IL-1β induced HAS mRNA expression and HA production more efficiently than TNF-α and IFN-γ. The exposition of the fibroblasts with the oxidant system markedly increased HAS activities while slightly HA production. The concomitant treatment of cells with the cytokines and the oxidant was able to further enhance, in a dose dependent way, with synergistic effect on HAS mRNA expression. On the contrary HA levels resulted unaffected by the concomitant treatment, and resemble those obtained with the exposure to FeSO4 plus ascorbate only. This lack in HA production could be due to the deleterious action of free radicals on the HA synthesis.


hyaluronanhyaluronan synthasescytokinesoxidative stressfibroblasts







extracellular matrix


hyaluronic acid


hyaluronan synthases


tumor necrosis factor alpha


interferon gamma


interleukin beta


reactive oxygen species


Dulbecco’s minimal essential medium


foetal bovine serum


reduced nicotinamide adenine dinucleotide


ethylenediaminetetraacetic acid


sodium dodecylsulphate


buffer phosphate saline


standard deviation

Copyright information

© Springer Science + Business Media, B.V. 2006

Authors and Affiliations

  • Giuseppe M. Campo
    • 1
    • 3
  • Angela Avenoso
    • 1
  • Salvatore Campo
    • 1
  • D'Ascola Angela
    • 1
  • Alida M. Ferlazzo
    • 2
  • Alberto Calatroni
    • 1
  1. 1.Department of Biochemical, Physiological and Nutritional Sciences, School of MedicineUniversity of Messina, Policlinico UniversitarioMessinaItaly
  2. 2.Department of Morphology, Biochemistry, Physiology and Animal Production, School of Veterinary MedicineUniversity of Messina, contrada AnnunziataMessinaItaly
  3. 3.PhD Department of Biochemical, Physiological and Nutritional Sciences, School of MedicineUniversity of Messina, Policlinico Universitario, Torre BiologicaMessinaItaly