Enhanced processing of APP induced by IL-1 beta can be reduced by indomethacin and nordihydroguaiaretic acid.
Abnormal processing of the amyloid precursor protein (APP) is thought to contribute to the formation of amyloid plaques in Alzheimer's disease. Several studies suggest that inflammation, and possibly the cytokines released during the inflammatory process, may participate in the plaque formation. We have utilized a cell culture system to examine the effects of the cytokine interleukin-1 beta (IL-1 beta) on the processing of APP. We present data to show that IL-1 beta increases the maturation of APP and causes enhanced processing of the full length APP isoforms. In addition, as reported previously in HUVEC cells, IL-1 beta increases the secretion of APP in PC12 cells. Indomethacin and NDGA, reported inhibitors of the cyclooxygenase and lipoxygenase pathways, respectively, block these effects, suggesting the involvement of prostaglandins and leukotrienes in IL-1 beta mediated APP processing.
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Department of Neurobiology and Anatomy University of Texas Health Science Center at Houston 77225.
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D000682:Amyloid / Q000378:metabolism*; D000818:Animals; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology*; D009637:Masoprocol / Q000494:pharmacology*; D016716:PC12 Cells; D011328:Prions; D011498:Protein Precursors / Q000378:metabolism*; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D051381:Rats
D000682:Amyloid; D007375:Interleukin-1; D011328:Prions; D011498:Protein Precursors; D009637:Masoprocol; D007213:Indomethacin