Sökning: onr:"swepub:oai:DiVA.org:umu-156597" > Inhibition of pSTAT...
Fältnamn | Indikatorer | Metadata |
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000 | 03815naa a2200445 4500 | |
001 | oai:DiVA.org:umu-156597 | |
003 | SwePub | |
008 | 190220s2019 | |||||||||||000 ||eng| | |
024 | 7 | a https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-1565972 URI |
024 | 7 | a https://doi.org/10.1186/s12950-019-0206-22 DOI |
040 | a (SwePub)umu | |
041 | a engb eng | |
042 | 9 SwePub | |
072 | 7 | a ref2 swepub-contenttype |
072 | 7 | a art2 swepub-publicationtype |
100 | 1 | a Perez-Baos, Sandra4 aut |
245 | 1 0 | a Inhibition of pSTAT1 by tofacitinib accounts for the early improvement of experimental chronic synovitis |
264 | c 2019-01-29 | |
264 | 1 | b BioMed Central (BMC),c 2019 |
338 | a electronic2 rdacarrier | |
520 | a Background: In order to gain insight into the early effects drawn by JAK inhibitors on intra-joint JAK/STAT-dependent signaling, we sought synovial activation of STATs and their end-products, along with their modification with tofacitinib (TOFA), at flare-up in antigen induced arthritis (AIA). New Zealand rabbits were randomly assigned to four groups –healthy controls, AIA, TOFA-treated AIA, or TOFA-treated controls–. AIA was induced with 4 weekly intra-articular ovalbumin injections in sensitized animals. TOFA (10 mg·kg− 1·day− 1) was administered for the last 2 weeks. Animals were euthanized 24 h after the last injection.Results: AIA animals showed high-grade synovitis, which was partially improved by TOFA. No effects of the treatment were found on serum C-reactive protein or on the synovial macrophage infiltration at this stage. Synovial MMP-1,-3 and -13 expression levels in treated AIA rabbits were found to drop to those of controls, while a downregulation of IL6, IFNγ and TNF was evident in treated versus untreated AIA rabbits. Concurrently, a reduction in pSTAT1 and SOCS1, but not in pSTAT3, SOCS3 or active NFκB-p65, was noted with TOFA.Conclusions: Studying the mechanism of action of immunomodulatory drugs represents a major challenge in vivo, since drug-dependent decreases in inflammation very likely mask direct effects on disease mechanisms. This study design allowed us to prevent any confounding effect resulting from reductions in the overall inflammatory status, hence assessing the true pharmacological actions of TOFA in a very severe synovitis. Our findings point to pSTAT1 and MMPs as early molecular readouts of response to this JAK inhibitor. | |
650 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Reumatologi och inflammation0 (SwePub)302102 hsv//swe |
650 | 7 | a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Rheumatology and Autoimmunity0 (SwePub)302102 hsv//eng |
653 | a Rheumatoid arthritis | |
653 | a Synovitis | |
653 | a Janus kinase inhibitors | |
653 | a Tofacitinib | |
700 | 1 | a Gratal, Paula4 aut |
700 | 1 | a Barrasa, Juan I.u Umeå universitet,Institutionen för molekylärbiologi (Medicinska fakulteten),Bone and Joint Research Unit, Rheumatology Department, IIS-Fundación Jiménez Díaz UAM, Avenida Reyes Católicos, 2. 28040, Madrid, Spain4 aut |
700 | 1 | a Lamuedra, Ana4 aut |
700 | 1 | a Sanchez-Pernaute, Olga4 aut |
700 | 1 | a Herrero-Beaumont, Gabriel4 aut |
700 | 1 | a Largo, Raquel4 aut |
710 | 2 | a Umeå universitetb Institutionen för molekylärbiologi (Medicinska fakulteten)4 org |
773 | 0 | t Journal of Inflammationd : BioMed Central (BMC)g 16q 16x 1476-9255 |
856 | 4 | u https://doi.org/10.1186/s12950-019-0206-2y Fulltext |
856 | 4 | u https://umu.diva-portal.org/smash/get/diva2:1290445/FULLTEXT01.pdfx primaryx Raw objecty fulltext:print |
856 | 4 | u https://doi.org/10.1186/s12950-019-0206-2 |
856 | 4 8 | u https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-156597 |
856 | 4 8 | u https://doi.org/10.1186/s12950-019-0206-2 |
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