Suppression of apoptotic cell death of IL-3-dependent cell lines by ER/SR Ca2+-ATPase inhibitors upon IL-3 deprivation.
An ER/SR Ca2+-ATPase inhibitor, cyclopiazonic acid (CPA), was found to suppress apoptotic cell death of IL-3-dependent cell lines, FDC.P2, IC-2, and Ba/F3, upon IL-3 deprivation. Structurally unrelated ER/SR Ca2+-ATPase inhibitors, thapsigargin and 2,5-di(tert-butyl)-1,4-benzohydroquinone also maintained cell viability in the absence of IL-3. In the Ca2+-free medium CPA failed to suppress apoptosis, suggesting that the anti-apoptotic activity of CPA is dependent on extracellular calcium. The culture supernatant of CPA-treated cells was able to prolong cell survival of FDC.P2 in the absence of IL-3. An anti-IL-4 antibody almost completely eliminated the anti-apoptotic activity of CPA. Indeed, a significant amount of IL-4 was detected in the supernatant of cells treated with ER/SR Ca2+-ATPase inhibitors. Thus, our present data clearly demonstrate not only that ER/SR Ca2+-ATPase inhibitors induce the secretion of IL-4 in IL-3-dependent cell lines, but also that IL-4 can replace IL-3 in protecting these cells from apoptotic cell death in an autocrine manner.
Department of Bioengineering, Tokyo Institute of Technology, Yokohama, Japan.
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Palaga
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Kataoka
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JT
Woo
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Nagai
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D017077:Culture Media, Conditioned; D004721:Endoplasmic Reticulum / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006873:Hydroquinones / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D007377:Interleukin-3 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000037:antagonists & inhibitors / Q000378:metabolism; D051379:Mice; D012519:Sarcoplasmic Reticulum / Q000201:enzymology; D019284:Thapsigargin / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D017077:Culture Media, Conditioned; D004791:Enzyme Inhibitors; D006873:Hydroquinones; D007211:Indoles; D007377:Interleukin-3; D015847:Interleukin-4; C019359:2,5-di-tert-butylhydroquinone; D019284:Thapsigargin; D000252:Calcium-Transporting ATPases; C000543:cyclopiazonic acid