CYTOKINE-REGULATED EXPRESSION OF PLATELET-DERIVED GROWTH-FACTOR GENE AND PROTEIN IN CULTURED HUMAN ASTROCYTES

To elucidate mechanisms regulating the production of platelet-derived growth factor (PDGF) in the CNS, we analyzed the influence of a panel of cytokines on PDGF mRNA and protein levels in astrocyte-enriched cul tures from the human embryonic brain and spinal cord. Using a specific ELISA, PDGF AB protein was detected in serum-free astrocyte supernata nts and its levels were significantly increased after treatment of the cultures with transforming growth factor-beta(1) (TGF-beta(1)) or tum or necrosis factor-alpha (TNF-alpha); the largest increase was detecte d after combined treatment with the two cytokines. Interleukin-1 beta (IL-1 beta) by itself had little or no effect but synergized with TGF- beta(1) in enhancing PDGF AB production. Supernatants from human astro cyte cultures stimulated the proliferation of rat oligodendrocyte prog enitors, and most of the mitogenic activity could be accounted for by PDGF. By northern blot analysis, both PDGF A- and PDGF B-chain mRNAs w ere detected in untreated astrocytes. PDGF B-chain mRNA levels were in creased by TGF-beta(1), TNF-alpha, TNF-alpha/TGF-beta(1), or IL-1 beta /TGF-beta(1), whereas PDGF A-chain mRNA levels were not consistently a ffected by cytokine treatments. These in vitro data indicate that TGF- beta(1), TNF-alpha, and IL-1 beta are able to stimulate astrocyte PDGF production. This cytokine network could play a role in CNS developmen t and repair after injury or inflammation.