Matches in SemOpenAlex for { <https://semopenalex.org/work/W2143205325> ?p ?o ?g. }
- W2143205325 abstract "T cell activation is associated with a rapid increase in intracellular fructose-2,6-bisphosphate (F2,6BP), an allosteric activator of the glycolytic enzyme, 6-phosphofructo-1-kinase. The steady state concentration of F2,6BP in T cells is dependent on the expression of the bifunctional 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatases (PFKFB1-4) and the fructose-2,6-bisphosphatase, TIGAR. Of the PFKFB family of enzymes, PFKFB3 has the highest kinase:bisphosphatase ratio and has been demonstrated to be required for T cell proliferation. A small molecule antagonist of PFKFB3, 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3PO), recently has been shown to reduce F2,6BP synthesis, glucose uptake and proliferation in transformed cells. We hypothesized that the induction of PFKFB3 expression may be required for the stimulation of glycolysis in T cells and that exposure to the PFKFB3 antagonist, 3PO, would suppress T cell activation.We examined PFKFB1-4 and TIGAR expression and F2,6BP concentration in purified CD3+ T cells stimulated with microbead-conjugated agonist antibodies specific for CD3 and the co-stimulatory receptor, CD28. We then determined the effect of 3PO on anti-CD3/anti-CD28-induced T cell activation, F2,6BP synthesis, 2-[1-14C]-deoxy-d-glucose uptake, lactate secretion, TNF-α secretion and proliferation. Finally, we examined the effect of 3PO administration on the development of delayed type hypersensitivity to methylated BSA and on imiquimod-induced psoriasis in mice.We found that purified human CD3+ T cells express PFKFB2, PFKFB3, PFKFB4 and TIGAR, and that anti-CD3/anti-CD28 conjugated microbeads stimulated a >20-fold increase in F2,6BP with a coincident increase in protein expression of the PFKFB3 family member and a decrease in TIGAR protein expression. We then found that exposure to the PFKFB3 small molecule antagonist, 3PO (1-10 μM), markedly attenuated the stimulation of F2,6BP synthesis, 2-[1-14C]-deoxy-D-glucose uptake, lactate secretion, TNF-α secretion and T cell aggregation and proliferation. We examined the in vivo effect of 3PO on the development of delayed type hypersensitivity to methylated BSA and on imiquimod-induced psoriasis in mice and found that 3PO suppressed the development of both T cell-dependent models of immunity in vivo.Our data demonstrate that inhibition of the PFKFB3 kinase activity attenuates the activation of T cells in vitro and suppresses T cell dependent immunity in vivo and indicate that small molecule antagonists of PFKFB3 may prove effective as T cell immunosuppressive agents." @default.
- W2143205325 created "2016-06-24" @default.
- W2143205325 creator A5020928977 @default.
- W2143205325 creator A5025818012 @default.
- W2143205325 creator A5041765132 @default.
- W2143205325 creator A5054078915 @default.
- W2143205325 creator A5071197441 @default.
- W2143205325 creator A5079892530 @default.
- W2143205325 creator A5086165685 @default.
- W2143205325 date "2012-05-16" @default.
- W2143205325 modified "2023-10-18" @default.
- W2143205325 title "Small molecule inhibition of 6-phosphofructo-2-kinase suppresses t cell activation" @default.
- W2143205325 cites W1503675015 @default.
- W2143205325 cites W1507021851 @default.
- W2143205325 cites W1594748719 @default.
- W2143205325 cites W1815191322 @default.
- W2143205325 cites W1905324622 @default.
- W2143205325 cites W1939997832 @default.
- W2143205325 cites W1966761605 @default.
- W2143205325 cites W1980284913 @default.
- W2143205325 cites W1982245720 @default.
- W2143205325 cites W1987708001 @default.
- W2143205325 cites W1989760304 @default.
- W2143205325 cites W2000081372 @default.
- W2143205325 cites W2000889838 @default.
- W2143205325 cites W2011034468 @default.
- W2143205325 cites W2011241671 @default.
- W2143205325 cites W2014573975 @default.
- W2143205325 cites W2024684558 @default.
- W2143205325 cites W2061610085 @default.
- W2143205325 cites W2068098843 @default.
- W2143205325 cites W2079854321 @default.
- W2143205325 cites W2095342914 @default.
- W2143205325 cites W2119239003 @default.
- W2143205325 cites W2125810931 @default.
- W2143205325 cites W2129424071 @default.
- W2143205325 cites W2138590199 @default.
- W2143205325 cites W2322803810 @default.
- W2143205325 cites W2561759163 @default.
- W2143205325 doi "https://doi.org/10.1186/1479-5876-10-95" @default.
- W2143205325 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3441391" @default.
- W2143205325 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/22591674" @default.
- W2143205325 hasPublicationYear "2012" @default.
- W2143205325 type Work @default.
- W2143205325 sameAs 2143205325 @default.
- W2143205325 citedByCount "69" @default.
- W2143205325 countsByYear W21432053252013 @default.
- W2143205325 countsByYear W21432053252014 @default.
- W2143205325 countsByYear W21432053252015 @default.
- W2143205325 countsByYear W21432053252016 @default.
- W2143205325 countsByYear W21432053252017 @default.
- W2143205325 countsByYear W21432053252018 @default.
- W2143205325 countsByYear W21432053252019 @default.
- W2143205325 countsByYear W21432053252020 @default.
- W2143205325 countsByYear W21432053252021 @default.
- W2143205325 countsByYear W21432053252022 @default.
- W2143205325 countsByYear W21432053252023 @default.
- W2143205325 crossrefType "journal-article" @default.
- W2143205325 hasAuthorship W2143205325A5020928977 @default.
- W2143205325 hasAuthorship W2143205325A5025818012 @default.
- W2143205325 hasAuthorship W2143205325A5041765132 @default.
- W2143205325 hasAuthorship W2143205325A5054078915 @default.
- W2143205325 hasAuthorship W2143205325A5071197441 @default.
- W2143205325 hasAuthorship W2143205325A5079892530 @default.
- W2143205325 hasAuthorship W2143205325A5086165685 @default.
- W2143205325 hasBestOaLocation W21432053251 @default.
- W2143205325 hasConcept C148125776 @default.
- W2143205325 hasConcept C153911025 @default.
- W2143205325 hasConcept C181199279 @default.
- W2143205325 hasConcept C185592680 @default.
- W2143205325 hasConcept C203014093 @default.
- W2143205325 hasConcept C2776090121 @default.
- W2143205325 hasConcept C55493867 @default.
- W2143205325 hasConcept C58431802 @default.
- W2143205325 hasConcept C79879829 @default.
- W2143205325 hasConcept C86803240 @default.
- W2143205325 hasConcept C8891405 @default.
- W2143205325 hasConceptScore W2143205325C148125776 @default.
- W2143205325 hasConceptScore W2143205325C153911025 @default.
- W2143205325 hasConceptScore W2143205325C181199279 @default.
- W2143205325 hasConceptScore W2143205325C185592680 @default.
- W2143205325 hasConceptScore W2143205325C203014093 @default.
- W2143205325 hasConceptScore W2143205325C2776090121 @default.
- W2143205325 hasConceptScore W2143205325C55493867 @default.
- W2143205325 hasConceptScore W2143205325C58431802 @default.
- W2143205325 hasConceptScore W2143205325C79879829 @default.
- W2143205325 hasConceptScore W2143205325C86803240 @default.
- W2143205325 hasConceptScore W2143205325C8891405 @default.
- W2143205325 hasIssue "1" @default.
- W2143205325 hasLocation W21432053251 @default.
- W2143205325 hasLocation W21432053252 @default.
- W2143205325 hasLocation W21432053253 @default.
- W2143205325 hasLocation W21432053254 @default.
- W2143205325 hasOpenAccess W2143205325 @default.
- W2143205325 hasPrimaryLocation W21432053251 @default.
- W2143205325 hasRelatedWork W1542374316 @default.
- W2143205325 hasRelatedWork W1592696248 @default.
- W2143205325 hasRelatedWork W1979841260 @default.
- W2143205325 hasRelatedWork W2005978956 @default.
- W2143205325 hasRelatedWork W2043153946 @default.