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Kmonickova E, Canova NK, Farghali H, Holy A, Zidek Z.
Modulator of intracellular Ca(2+), Thapsigargin, interferes with
in vitro secretion of cytokines and nitric oxide.
Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2005
Dec;149(2):321-4.
Interference of thapsigargin , an inhibitor of
endoplasmic reticulum Ca(2+) ATPase, with immune reactivity of
murine macrophages was investigated under conditions in vitro.
The activation of cells with lipopolysaccharide (LPS),
interferon-(gamma) (IFN-(gamma)), and with acyclic nucleoside
phosphonate N(6)-isobutyl-9-[2-(phosphonomethoxy)ethyl]-
2,6-diaminopurine (N(6)-isobutyl-PMEDAP) resulted in enhanced
production of cytokines TNF-alpha, IL-10, chemokines RANTES/CCL5
and MIP-1alpha/CCL3, as well as in substantially augmented
production of nitric oxide (NO) triggered by IFN-(gamma). The
effects were in a dual mode of action influenced by thapsigargin
(1 microM). While thapsigargin upregulated secretion of
TNF-alpha, it inhibited secretion of IL-10 and RANTES. The
immune-stimulated secretion of MIP-1alpha remained virtually
unaffected, though thapsigargin on its own activated expression
of MIP-1alpha in macrophages. The high-output NO production
induced by IFN-(gamma), high concentrations of LPS, or by
combination of IFN-(gamma) plus LPS or N(6)-isobutyl-PMEDAP was
inhibited by thapsigargin. On the other hand, production of NO
which was marginally activated by low concentration of LPS was
upregulated by thapsigargin.
PMID: 16601780 |
