Inflammatory molecule release by beta-amyloid-treated T98G astrocytoma cells: role of prostaglandins and modulation by paracetamol.
Deposition of beta-amyloid in the brain triggers an inflammatory response which accompanies the neuropathologic events of Alzheimer's disease and contributes to the destruction of brain tissue. The present study shows that beta-amyloid can stimulate human astrocytoma cells (T98G) to secrete the proinflammatory factors interleukin-6 and prostaglandins. Furthermore, prostaglandins can stimulate T98G to secrete interleukin-6, which in turn triggers the formation of additional prostaglandins. Prostaglandins are, therefore, a key element in the induction and maintenance of a state of chronic inflammation in the brain which may exacerbate the fundamental pathology in Alzheimer patients. Paracetamol (0.01-1000 microM), an unusual analgesic/antipyretic drug which acts preferentially by reducing prostaglandin production within the central nervous system, and indomethacin (0.001-10 microM) caused a clear dose-dependent reduction of prostaglandin E2 production by stimulated T98G cells whereas interleukin-6 release was not affected. These data provide further evidence of the involvement of non-steroidal anti-inflammatory drugs in the inflammatory processes that can be generated by glial cells in intact brain.
Landolfi
C
C
Angelini Ricerche, Pomezia, Rome, Italy.
Soldo
L
L
Polenzani
L
L
Apicella
C
C
Capezzone de Joannon
A
A
Coletta
I
I
Di Cesare
F
F
Brufani
M
M
Pinza
M
M
Milanese
C
C
D000082:Acetaminophen / Q000494:pharmacology; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology; D001254:Astrocytoma; D017077:Culture Media, Conditioned / Q000032:analysis / Q000378:metabolism; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism* / Q000494:pharmacology; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D007527:Isoenzymes / Q000235:genetics; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics; D011453:Prostaglandins / Q000494:pharmacology / Q000502:physiology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D016229:Amyloid beta-Peptides; D018712:Analgesics, Non-Narcotic; D017077:Culture Media, Conditioned; D018836:Inflammation Mediators; D007375:Interleukin-1; D015850:Interleukin-6; D007527:Isoenzymes; D008565:Membrane Proteins; D011453:Prostaglandins; D012333:RNA, Messenger; D000082:Acetaminophen; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone