Cytokine-induced production of macrophage inflammatory protein-1α (MIP-1α) in cultured human astrocytes

Macrophage inflammatory protein-1 alpha (MIP-1 alpha) is a member of a superfamily of inflammatory cytokines termed chemokines, and it has been implicated in the pathogenesis of several human diseases with inflammatory components. It has been known that MIP-1 alpha. plays a role in recruiting and activating mononuclear phagocytes in the central nervous system (CNS), and that astrocytes and microglia are sources of this chemokine, However, details of the regulation of MIP-1 alpha production by these glial cells are not known. In the present study, expression of MIP-lcr was determined in purified cultures of human astrocyte, MIP-1 alpha mRNA levels in human astrocyte cell preparations were determined by reverse trascription polymerase chain reaction (RT-PCR) and amount of MIP-1 alpha protein secreted into culture supernatants by human astrocytes was assayed by enzyme-linked immunosorbent assay (ELISA), Under the unstimulated conditions, human astrocytes did not express MIP-1 alpha message or protein, indicating that human astrocytes do not constitutively carry MIP-1 alpha. message. Following treatment with interleukin-1 beta (IL-1 beta), human astrocytes demonstrated increased message and protein expression for MIP-1 alpha, while other immune modulators such as interferon-gamma (IFN)-gamma, tumor necrosis factor-alpha (TNF-alpha), granulocyte-macrophage colony-stimulating factor (GM-CSF), lipopolysaccharide, or phorbol ester (a protein kinase C activator) did not induce MIP-1 alpha, expression in human astrocytes. J. Neurosci. Res. 55:245-251, 1999. (C) 1999 Wiley-Liss, Inc.