The Journal of Immunology, Vol 152, Issue 10 5022-5031, Copyright © 1994 by American Association of Immunologists

ARTICLES

Regulation of leukemia inhibitory factor synthesis in cultured human astrocytes

F Aloisi, S Rosa, U Testa, P Bonsi, G Russo, C Peschle and G Levi
Laboratory of Organ and System Pathophysiology, National Institute of Health, Rome, Italy.

We have examined the ability of human astrocytes to synthesize and secrete leukemia inhibitory factor (LIF), which is a multifunctional cytokine that controls cell proliferation and differentiation in many tissues, including the nervous system. Astrocyte-enriched cultures, prepared from 8- to 9-wk-old embryonic brains, expressed LIF mRNA and secreted LIF protein. LIF synthesis was significantly increased by the cytokines IL-1 beta, TNF-alpha, and TGF-beta 1, but not by IFN-gamma, IL-6, or LPS. No major differences in basal and cytokine-inducible LIF production were detected among astrocyte populations obtained from different brain areas. LIF synthesis was lower in serum-free than in serum-containing astrocyte cultures. A role for protein kinase C in the regulation of astrocyte LIF production was suggested by the findings that phorbol esters induced both LIF mRNA and protein and that the cytokine-induced LIF increase was partially antagonized by relatively selective inhibitors of protein kinase C such as H7 and staurosporine. Human leptomeningeal fibroblasts also expressed LIF gene and protein. Astrocytes produced LIF and responded to cytokines with increased LIF synthesis only after being subcultured, and not when grown in primary cultures in close contact with neurons. Our findings suggest that in vivo induction of astrocyte LIF secretion might occur in pathologic conditions as a consequence of both alterations of neuronal-glial interactions and a local increase in the level of inflammatory cytokines.

This article has been cited by other articles:

				Z. Kornyei, E. Gocza, R. Ruhl, B. Orsolits, E. Voros, B. Szabo, B. Vagovits, and E. Madarasz Astroglia-derived retinoic acid is a key factor in glia-induced neurogenesis FASEB J, August 1, 2007; 21(10): 2496 - 2509. [Abstract] [Full Text] [PDF]

				W. Allaerts and H. Vankelecom History and perspectives of pituitary folliculo-stellate cell research Eur. J. Endocrinol., July 1, 2005; 153(1): 1 - 12. [Abstract] [Full Text] [PDF]

				H. Boeuf, K. Merienne, S. Jacquot, D. Duval, M. Zeniou, C. Hauss, B. Reinhardt, Y. Huss-Garcia, A. Dierich, D. A. Frank, et al. The Ribosomal S6 Kinases, cAMP-responsive Element-binding, and STAT3 Proteins Are Regulated by Different Leukemia Inhibitory Factor Signaling Pathways in Mouse Embryonic Stem Cells J. Biol. Chem., November 30, 2001; 276(49): 46204 - 46211. [Abstract] [Full Text] [PDF]

				R. P. Mohney and R. E. Zigmond Vasoactive Intestinal Peptide Enhances Its Own Expression in Sympathetic Neurons after Injury J. Neurosci., July 15, 1998; 18(14): 5285 - 5293. [Abstract] [Full Text] [PDF]

				T. Kordula, R. E. Rydel, E. F. Brigham, F. Horn, P. C. Heinrich, and J. Travis Oncostatin M and the Interleukin-6 and Soluble Interleukin-6 Receptor Complex Regulate alpha 1-Antichymotrypsin Expression in Human Cortical Astrocytes J. Biol. Chem., February 13, 1998; 273(7): 4112 - 4118. [Abstract] [Full Text] [PDF]

				A. Gard, M. Burrell, S. Pfeiffer, J. Rudge, and W. Williams Astroglial control of oligodendrocyte survival mediated by PDGF and leukemia inhibitory factor-like protein Development, January 7, 1995; 121(7): 2187 - 2197. [Abstract] [PDF]

				C. Ware, M. Horowitz, B. Renshaw, J. Hunt, D Liggitt, S. Koblar, B. Gliniak, H. McKenna, T Papayannopoulou, B Thoma, et al. Targeted disruption of the low-affinity leukemia inhibitory factor receptor gene causes placental, skeletal, neural and metabolic defects and results in perinatal death Development, January 5, 1995; 121(5): 1283 - 1299. [Abstract] [PDF]