|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
1
|
|
pubmed:dateCreated |
2006-6-20
|
|
pubmed:abstractText |
Recently, glycogen synthase kinase-3 (GSK-3) has being identified as an ubiquitous serine-threonine protein kinase that participates in a multitude of cellular processes and plays an important role in the pathophysiology of a number of diseases. The aim of this study was to investigate the effects of GSK-3beta inhibition on the degree of arthritis caused by type II collagen (CII) in the mouse (collagen-induced arthritis; CIA). Mice developed erosive hind paw arthritis when immunized with CII in an emulsion in complete Freund's adjuvant (CFA). The incidence of CIA was 100% by day 28 in the CII-challenged mice and the severity of CIA progressed over a 35-day period with radiographic evaluation revealing focal resorption of bone. The histopathology of CIA included erosion of the cartilage at the joint margins. Treatment of mice with the GSK-3beta inhibitor TDZD-8 (1 mg/kg/day i.p.) starting at the onset of arthritis (day 25) ameliorated the clinical signs at days 26-35 and improved histological status in the joint and paw. Immunohistochemical analysis for nitrotyrosine, poly(ADP-ribose) (PAR), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) revealed a positive staining in inflamed joints from mice subjected to CIA. The degree of staining for nitrotyrosine, PAR, iNOS, and COX-2 was significantly reduced in CII-challenged mice treated with the GSK-3beta inhibitor. Plasma levels of tumor necrosis factor (TNF)-alpha and the joint tissue levels of macrophage inflammatory protein (MIP)-1alpha and MIP-2 were also significantly reduced by GSK-3beta inhibition. These data demonstrate that GSK-3beta inhibition exerts an anti-inflammatory effect during chronic inflammation and is able to ameliorate the tissue damage associated with CIA.
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/3-nitrotyrosine,
http://linkedlifedata.com/resource/pubmed/chemical/4-benzyl-2-methyl-1,2,4-thiadiazolid...,
http://linkedlifedata.com/resource/pubmed/chemical/Chemokine CCL3,
http://linkedlifedata.com/resource/pubmed/chemical/Chemokine CCL4,
http://linkedlifedata.com/resource/pubmed/chemical/Chemokine CXCL2,
http://linkedlifedata.com/resource/pubmed/chemical/Collagen Type II,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclooxygenase 2,
http://linkedlifedata.com/resource/pubmed/chemical/Glycogen Synthase Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-6,
http://linkedlifedata.com/resource/pubmed/chemical/Macrophage Inflammatory Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Monokines,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Synthase Type II,
http://linkedlifedata.com/resource/pubmed/chemical/Poly(ADP-ribose) Polymerases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Thiadiazoles,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Tyrosine,
http://linkedlifedata.com/resource/pubmed/chemical/glycogen synthase kinase 3 beta
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Jul
|
|
pubmed:issn |
1521-6616
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:volume |
120
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
57-67
|
|
pubmed:dateRevised |
2011-11-2
|
|
pubmed:meshHeading |
pubmed-meshheading:16631408-Animals,
pubmed-meshheading:16631408-Arthritis, Experimental,
pubmed-meshheading:16631408-Arthritis, Rheumatoid,
pubmed-meshheading:16631408-Chemokine CCL3,
pubmed-meshheading:16631408-Chemokine CCL4,
pubmed-meshheading:16631408-Chemokine CXCL2,
pubmed-meshheading:16631408-Collagen Type II,
pubmed-meshheading:16631408-Cyclooxygenase 2,
pubmed-meshheading:16631408-Glycogen Synthase Kinase 3,
pubmed-meshheading:16631408-Hindlimb,
pubmed-meshheading:16631408-Interleukin-6,
pubmed-meshheading:16631408-Leukocyte Count,
pubmed-meshheading:16631408-Macrophage Inflammatory Proteins,
pubmed-meshheading:16631408-Mice,
pubmed-meshheading:16631408-Mice, Inbred DBA,
pubmed-meshheading:16631408-Monokines,
pubmed-meshheading:16631408-Nitric Oxide Synthase Type II,
pubmed-meshheading:16631408-Poly(ADP-ribose) Polymerases,
pubmed-meshheading:16631408-Protein Kinase Inhibitors,
pubmed-meshheading:16631408-Thiadiazoles,
pubmed-meshheading:16631408-Tumor Necrosis Factor-alpha,
pubmed-meshheading:16631408-Tyrosine
|
|
pubmed:year |
2006
|
|
pubmed:articleTitle |
Glycogen synthase kinase-3beta inhibition attenuates the degree of arthritis caused by type II collagen in the mouse.
|
|
pubmed:affiliation |
Institute of Pharmacology, School of Medicine, University of Messina, Torre Biologica-Policlinico Universitario, Via C. Valeria-Gazzi-98100 Messina, Italy. salvator@unime.it
|
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|
