PMID- 16601780
OWN - NLM
STAT- MEDLINE
DCOM- 20070828
LR  - 20191210
IS  - 1213-8118 (Print)
IS  - 1213-8118 (Linking)
VI  - 149
IP  - 2
DP  - 2005 Dec
TI  - Modulator of intracellular Ca(2+), thapsigargin, interferes with in vitro 
      secretion of cytokines and nitric oxide.
PG  - 321-4
AB  - Interference of thapsigargin (TG), 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 TG (1 microM). While TG upregulated 
      secretion of TNF-alpha, it inhibited secretion of IL-10 and RANTES. The 
      immune-stimulated secretion of MIP-1alpha remained virtually unaffected, though 
      TG 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 TG. 
      On the other hand, production of NO which was marginally activated by low 
      concentration of LPS was upregulated by TG.
FAU - Kmonickova, Eva
AU  - Kmonickova E
AD  - Institute of Experimental Medicine, Academy of Sciences, Prague, Czech Republic. 
      kmonickova@biomed.cas.cz
FAU - Canova, Nikolina Kutinova
AU  - Canova NK
FAU - Farghali, Hassan
AU  - Farghali H
FAU - Holy, Antonin
AU  - Holy A
FAU - Zidek, Zdenek
AU  - Zidek Z
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Czech Republic
TA  - Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub
JT  - Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, 
      Czechoslovakia
JID - 101140142
RN  - 0 (Cytokines)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 5EX1YUR4DH (9-(2-phosphonylmethoxyethyl)-2,6-diaminopurine)
RN  - 67526-95-8 (Thapsigargin)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 7.2.2.10 (Calcium-Transporting ATPases)
RN  - GAN16C9B8O (Glutathione)
RN  - JAC85A2161 (Adenine)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Adenine/analogs & derivatives/pharmacology
MH  - Animals
MH  - Calcium/*metabolism
MH  - Calcium-Transporting ATPases/antagonists & inhibitors
MH  - Cells, Cultured
MH  - Cytokines/*biosynthesis
MH  - Endoplasmic Reticulum/metabolism
MH  - Enzyme Inhibitors/pharmacology
MH  - Female
MH  - Glutathione/metabolism
MH  - Immunosuppressive Agents/pharmacology
MH  - Interferon-gamma/pharmacology
MH  - Lipopolysaccharides/pharmacology
MH  - Macrophages/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Nitric Oxide/*biosynthesis
MH  - Thapsigargin/*pharmacology
MH  - Tumor Necrosis Factor-alpha/biosynthesis
EDAT- 2006/04/08 09:00
MHDA- 2007/08/29 09:00
CRDT- 2006/04/08 09:00
PHST- 2006/04/08 09:00 [pubmed]
PHST- 2007/08/29 09:00 [medline]
PHST- 2006/04/08 09:00 [entrez]
PST - ppublish
SO  - Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2005 Dec;149(2):321-4.