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 cultures from the human embryonic brain and spinal cord. Using a specific ELISA, PDGF, AB protein was detected in serum-free astrocyte supernatants and its levels were significantly increased after treatment of the cultures with transforming growth factor-beta 1 (TGF-beta 1) or tumor necrosis factor-alpha (TNF-alpha); the largest increase was detected after combined treatment with the two cytokines. Interleukin-1beta (IL-1beta) by itself had little or no effect but synergized with TGF-beta 1 in enhancing PDGF AB production. Supernatants from human astrocyte cultures stimulated the proliferation of rat oligodendrocyte progenitors, and most of the mitogenic activity could be accounted for by PDGF. By northern blot analysis, both PDGF A- and PDGF B- chains mRNAs were detected in untreated astrocytes. PDGF B-chain mRNA levels were increased by TGF-beta 1, TNF-alpha, TNF-alpha/TGF-beta, or IL-1-beta/TGF-beta 1, whereas PDGF A-chain mRNA levels were not consistently affected 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 development and repair after injury or inflammation.
Silberstein
F C
FC
Laboratory of Organ and System Pathophysiology, Istituto Superiore di Sanità, Rome, Italy.
De Simone
R
R
Levi
G
G
Aloisi
F
F
D001253:Astrocytes / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D001921:Brain / Q000166:cytology / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured / Q000201:enzymology / Q000502:physiology; D016207:Cytokines / Q000494:pharmacology*; D004622:Embryo, Mammalian / Q000166:cytology; D005786:Gene Expression Regulation; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D009836:Oligodendroglia / Q000166:cytology / Q000187:drug effects; D010982:Platelet-Derived Growth Factor / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology / Q000502:physiology; D013234:Stem Cells / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016207:Cytokines; D007375:Interleukin-1; D010982:Platelet-Derived Growth Factor; D011518:Proto-Oncogene Proteins; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; C075278:platelet-derived growth factor A; D011505:Protein-Tyrosine Kinases