IL-1-BETA AND TNF-ALPHA, BUT NOT IL-6, INDUCE ALPHA(1)-ANTICHYMOTRYPSIN EXPRESSION IN THE HUMAN ASTROCYTOMA CELL-LINE U373 MG

CYTOKINES such as interleukin-l (IL-1) and interleukin-6 (IL-6) have p reviously been shown to participate in neurodegenerative processes inc luding Alzheimer's disease. However, the molecular consequences of inc reased cytokine expression in the brain remain largely unknown. We hav e studied the effects of IL-1, IL-6 and TNF alpha: on the expression o f the acute-phase protein alpha(1)-urantichymotrypsin (ACT) in human a strocytoma cell lines. Both IL-1 and TNF alpha, but not IL-6, were abl e to induce ACT gene transcription and protein synthesis. The syntheti c glucocorticoid dexamethasone enhanced cytokine-induced ACT mRNA expr ession and protein synthesis. We conclude that IL-l-induced expression of ACT may be part of the inflammatory response in the brain and may be involved in the pathology of Alzheimer's disease.