TY - JOUR
T1 - Astrocyte expression of monocyte chemoattractant protein-1 is differentially regulated by transforming growth factor beta
AU - Weiss, Jonathan M.
AU - Berman, Joan W.
N1 - Funding Information:
This work was supported, in part, by NIMH Grant MH52974 and NIH Grants 11920 and 5T32CA09173. The FACS facility at the Albert Einstein College of Medicine is supported, in part, by NCI Cancer Center Support Grant #5P30-CA13330. We thank Drs. Hsiao-Nan Hao and Karen Weidenheim for providing the fetal tissue used in these experiments and Dr. C. Chang for assistance with the statistical analyses. We thank Dr. Celia Brosnan for her most helpful discussions and Dr. Tina Calderon and Neelufar Mozaffarian for their critical reading of this manuscript. This manuscript is in partial fulfilment for the degree of Doctor of Philosophy from the Sue Golding Graduate Division of the Albert Einstein College of Medicine for J.M.W.
PY - 1998/11/2
Y1 - 1998/11/2
N2 - The pathophysiology of central nervous system (CNS) inflammatory disease is dependent, in part, on leukocyte recruitment across the blood-brain barrier. The expression of cytokines and chemokines by astrocytes may contribute to this process. Astrocytes express monocyte chemoattractant protein-1 (MCP-1), an activator of monocytes and a chemoattractant for monocytes and activated T cells. We examined the regulation of MCP-1 expression in human fetal astrocytes following cytokine treatment in the presence and absence of transforming growth factor beta (TGF-β). TGF-β, TNFα and IL-1β, but not IFNγ, induced MCP-1 mRNA and protein, TGF-β, in cotreatment with TNFα caused an additive increase in MCP-1 mRNA, but not protein. In combination with IFNγ, TGF-β significantly increased MCP-1 mRNA and protein, as compared to either untreated, TGF-β or IFNγ-treated astrocytes. However, TGF-β in cotreatment with IL-1β decreased MCP-1 mRNA and protein, as compared to IL-1β alone. Treatment of astrocytes with TGF- β prior to TNFα, IFNγ or IL-1β treatment significantly increased MCP-1 expression. The kinetics of cytokine expression in the CNS may differentially regulate astrocyte-derived MCP-1 expression and subsequent recruitment and activation of leukocytes.
AB - The pathophysiology of central nervous system (CNS) inflammatory disease is dependent, in part, on leukocyte recruitment across the blood-brain barrier. The expression of cytokines and chemokines by astrocytes may contribute to this process. Astrocytes express monocyte chemoattractant protein-1 (MCP-1), an activator of monocytes and a chemoattractant for monocytes and activated T cells. We examined the regulation of MCP-1 expression in human fetal astrocytes following cytokine treatment in the presence and absence of transforming growth factor beta (TGF-β). TGF-β, TNFα and IL-1β, but not IFNγ, induced MCP-1 mRNA and protein, TGF-β, in cotreatment with TNFα caused an additive increase in MCP-1 mRNA, but not protein. In combination with IFNγ, TGF-β significantly increased MCP-1 mRNA and protein, as compared to either untreated, TGF-β or IFNγ-treated astrocytes. However, TGF-β in cotreatment with IL-1β decreased MCP-1 mRNA and protein, as compared to IL-1β alone. Treatment of astrocytes with TGF- β prior to TNFα, IFNγ or IL-1β treatment significantly increased MCP-1 expression. The kinetics of cytokine expression in the CNS may differentially regulate astrocyte-derived MCP-1 expression and subsequent recruitment and activation of leukocytes.
KW - Astrocytes
KW - Monocyte chemoattractant protein-1
KW - Transforming growth factor beta
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U2 - 10.1016/S0165-5728(98)00183-0
DO - 10.1016/S0165-5728(98)00183-0
M3 - Article
C2 - 9846835
AN - SCOPUS:0032476641
SN - 0165-5728
VL - 91
SP - 190
EP - 197
JO - Journal of Neuroimmunology
JF - Journal of Neuroimmunology
IS - 1-2
ER -
