Cytokine-induced production of macrophage inflammatory protein-1alpha (MIP-1alpha) in cultured human astrocytes.
Macrophage inflammatory protein-1alpha (MIP-1alpha) 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-1alpha 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-1alpha production by these glial cells are not known. In the present study, expression of MIP-1alpha was determined in purified cultures of human astrocyte. MIP-1alpha mRNA levels in human astrocyte cell preparations were determined by reverse transcription polymerase chain reaction (RT-PCR) and amount of MIP-1alpha 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-1alpha message or protein, indicating that human astrocytes do not constitutively carry MIP-1alpha message. Following treatment with interleukin-1beta (IL-1beta), human astrocytes demonstrated increased message and protein expression for MIP-1alpha, 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-1alpha expression in human astrocytes.
Miyamoto
Y
Y
Department of Medicine, University of British Columbia, Vancouver, Canada.
Kim
S U
SU
D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D016207:Cytokines / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013268:Stimulation, Chemical