FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3204231006> ?p ?o ?g. }

• W3204231006 abstract "Current knowledge on the actions of tofacitinib on cytokine signaling pathways in rheumatoid arthritis (RA) is based on in vitro studies. Our study is the first to examine the effects of tofacitinib treatment on Janus kinase (JAK) - signal transducer and activator of transcription (STAT) pathways in vivo in patients with RA.Sixteen patients with active RA, despite treatment with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), received tofacitinib 5 mg twice daily for three months. Levels of constitutive and cytokine-induced phosphorylated STATs in peripheral blood monocytes, T cells and B cells were measured by flow cytometry at baseline and three-month visits. mRNA expression of JAKs, STATs and suppressors of cytokine signaling (SOCS) were measured from peripheral blood mononuclear cells (PBMCs) by quantitative PCR. Association of baseline signaling profile with treatment response was also investigated.Tofacitinib, in csDMARDs background, decreased median disease activity score (DAS28) from 4.4 to 2.6 (p < 0.001). Tofacitinib treatment significantly decreased cytokine-induced phosphorylation of all JAK-STAT pathways studied. However, the magnitude of the inhibitory effect depended on the cytokine and cell type studied, varying from 10% to 73% inhibition following 3-month treatment with tofacitinib. In general, strongest inhibition by tofacitinib was observed with STAT phosphorylations induced by cytokines signaling through the common-γ-chain cytokine receptor in T cells, while lowest inhibition was demonstrated for IL-10 -induced STAT3 phosphorylation in monocytes. Constitutive STAT1, STAT3, STAT4 and STAT5 phosphorylation in monocytes and/or T cells was also downregulated by tofacitinib. Tofacitinib treatment downregulated the expression of several JAK-STAT pathway components in PBMCs, SOCSs showing the strongest downregulation. Baseline STAT phosphorylation levels in T cells and monocytes and SOCS3 expression in PBMCs correlated with treatment response.Tofacitinib suppresses multiple JAK-STAT pathways in cytokine and cell population specific manner in RA patients in vivo. Besides directly inhibiting JAK activation, tofacitinib downregulates the expression of JAK-STAT pathway components. This may modulate the effects of tofacitinib on JAK-STAT pathway activation in vivo and explain some of the differential findings between the current study and previous in vitro studies. Finally, baseline immunological markers associate with the treatment response to tofacitinib." @default.
• W3204231006 created "2021-10-11" @default.
• W3204231006 creator A5006623618 @default.
• W3204231006 creator A5014117301 @default.
• W3204231006 creator A5024144901 @default.
• W3204231006 creator A5029039417 @default.
• W3204231006 creator A5034562303 @default.
• W3204231006 creator A5042453652 @default.
• W3204231006 creator A5051696625 @default.
• W3204231006 creator A5057213310 @default.
• W3204231006 creator A5067508775 @default.
• W3204231006 creator A5083669558 @default.
• W3204231006 date "2021-09-24" @default.
• W3204231006 modified "2023-10-15" @default.
• W3204231006 title "Tofacitinib Suppresses Several JAK-STAT Pathways in Rheumatoid Arthritis In Vivo and Baseline Signaling Profile Associates With Treatment Response" @default.
• W3204231006 cites W114839291 @default.
• W3204231006 cites W1549169543 @default.
• W3204231006 cites W1553660565 @default.
• W3204231006 cites W1995629248 @default.
• W3204231006 cites W2063265278 @default.
• W3204231006 cites W2069302785 @default.
• W3204231006 cites W2069305891 @default.
• W3204231006 cites W2093811818 @default.
• W3204231006 cites W2098584805 @default.
• W3204231006 cites W2116558079 @default.
• W3204231006 cites W2118767323 @default.
• W3204231006 cites W2121219094 @default.
• W3204231006 cites W2124345149 @default.
• W3204231006 cites W2131599301 @default.
• W3204231006 cites W2135694095 @default.
• W3204231006 cites W2138609584 @default.
• W3204231006 cites W2140559651 @default.
• W3204231006 cites W2164291698 @default.
• W3204231006 cites W2168781986 @default.
• W3204231006 cites W2195835569 @default.
• W3204231006 cites W2257779930 @default.
• W3204231006 cites W2270670296 @default.
• W3204231006 cites W2298448428 @default.
• W3204231006 cites W2560587756 @default.
• W3204231006 cites W2561978143 @default.
• W3204231006 cites W2601742683 @default.
• W3204231006 cites W2609592632 @default.
• W3204231006 cites W2761516325 @default.
• W3204231006 cites W2889444842 @default.
• W3204231006 cites W2896491161 @default.
• W3204231006 cites W2912100582 @default.
• W3204231006 cites W2912641147 @default.
• W3204231006 cites W2914209107 @default.
• W3204231006 cites W2916037465 @default.
• W3204231006 cites W2966093740 @default.
• W3204231006 cites W2988722150 @default.
• W3204231006 cites W2995869498 @default.
• W3204231006 cites W3097229464 @default.
• W3204231006 cites W3136549884 @default.
• W3204231006 cites W4211111012 @default.
• W3204231006 doi "https://doi.org/10.3389/fimmu.2021.738481" @default.
• W3204231006 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/8498592" @default.
• W3204231006 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/34630419" @default.
• W3204231006 hasPublicationYear "2021" @default.
• W3204231006 type Work @default.
• W3204231006 sameAs 3204231006 @default.
• W3204231006 citedByCount "20" @default.
• W3204231006 countsByYear W32042310062022 @default.
• W3204231006 countsByYear W32042310062023 @default.
• W3204231006 crossrefType "journal-article" @default.
• W3204231006 hasAuthorship W3204231006A5006623618 @default.
• W3204231006 hasAuthorship W3204231006A5014117301 @default.
• W3204231006 hasAuthorship W3204231006A5024144901 @default.
• W3204231006 hasAuthorship W3204231006A5029039417 @default.
• W3204231006 hasAuthorship W3204231006A5034562303 @default.
• W3204231006 hasAuthorship W3204231006A5042453652 @default.
• W3204231006 hasAuthorship W3204231006A5051696625 @default.
• W3204231006 hasAuthorship W3204231006A5057213310 @default.
• W3204231006 hasAuthorship W3204231006A5067508775 @default.
• W3204231006 hasAuthorship W3204231006A5083669558 @default.
• W3204231006 hasBestOaLocation W32042310061 @default.
• W3204231006 hasConcept C112392421 @default.
• W3204231006 hasConcept C126322002 @default.
• W3204231006 hasConcept C170493617 @default.
• W3204231006 hasConcept C171958077 @default.
• W3204231006 hasConcept C203014093 @default.
• W3204231006 hasConcept C2775855021 @default.
• W3204231006 hasConcept C2777575956 @default.
• W3204231006 hasConcept C2778277574 @default.
• W3204231006 hasConcept C2778690821 @default.
• W3204231006 hasConcept C2778886723 @default.
• W3204231006 hasConcept C2778923194 @default.
• W3204231006 hasConcept C2779391668 @default.
• W3204231006 hasConcept C502942594 @default.
• W3204231006 hasConcept C62478195 @default.
• W3204231006 hasConcept C65439459 @default.
• W3204231006 hasConcept C71924100 @default.
• W3204231006 hasConcept C86803240 @default.
• W3204231006 hasConcept C95444343 @default.
• W3204231006 hasConcept C98274493 @default.
• W3204231006 hasConceptScore W3204231006C112392421 @default.
• W3204231006 hasConceptScore W3204231006C126322002 @default.
• W3204231006 hasConceptScore W3204231006C170493617 @default.
• W3204231006 hasConceptScore W3204231006C171958077 @default.
• W3204231006 hasConceptScore W3204231006C203014093 @default.

• next