TNFalpha Inhibits Schwann Cell Proliferation, Connexin46 Expression, and Gap Junctional Communication

Author： Chandross K.J. Spray D.C. Cohen R.I. Kumar N.M. Kremer M. dermietzel R. Kessler J.A.

ISSN： 1044-7431

Source： Molecular and Cellular Neuroscience, Vol.7, Iss.6, 1996-06, pp. : 479-500

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Abstract

Schwann cell responses to nerve injury are stimulated, in part, by inflammatory cytokines. This study compares changes in the phenotype of cultured Schwann cells after exposure to the cytokine tumor necrosis factor (TNF)-alpha or the mitogen neu differentiation factor (NDF)-beta. TNFalpha inhibited proliferation in a dose-dependent manner without altering Schwann cell survival. TNFalpha also reduced both gap junctional conductance and Lucifer yellow dye coupling between Schwann cells. Moreover, both P 0 and glial fibrillary acidic protein (GFAP) immunoreactivity were reduced. By contrast, NDFbeta initially had little effect on cell division although it reduced junctional coupling within 8 h. However, by 48 h, NDFbeta stimulated proliferation with a concomitant increase in coupling. Dividing Schwann cells (BrdU + ) were preferentially dye coupled compared to nondividing cells, indicating an association between proliferation and coupling. Moreover, cultured Schwann cells expressed connexin46 mRNA and protein, and changes in the levels of the protein correlated with the degree of proliferation and coupling. The data thus provide evidence for cytokine-induced modulation of Schwann cell antigenic phenotype, proliferation, and gap junction properties. These observations suggest that enhanced gap junctional communication among Schwann cells after nerve injury could help to coordinate cellular responses to the injury, and that TNFalpha may be a signal which terminates proliferation as well as junctional communication.