Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
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Target Concepts:
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Query: UMLS:C0027121 (
myositis
)
4,538
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Idiopathic inflammatory myopathy is a chronic inflammatory muscle disease characterized by mononuclear cell infiltration in the skeletal muscle. The infiltrated inflammatory cells express various cytokines and cytotoxic molecules. Chemokines are thought to contribute to the inflammatory cell migration into the muscle. We induced experimental autoimmune
myositis
(EAM) in SJL/J mice by immunization with rabbit myosin and CFA. In the affected muscles of EAM mice, CX3CL1 (fractalkine) was expressed on the infiltrated mononuclear cells and endothelial cells, and its corresponding receptor,
CX3CR1
, was expressed on the infiltrated CD4 and CD8 T cells and macrophages. Treatment of EAM mice with anti-CX3CL1 mAb significantly reduced the histopathological
myositis
score, the number of necrotic muscle fibers, and infiltration of CD4 and CD8 T cells and macrophages. Furthermore, treatment with anti-CX3CL1 mAb down-regulated the mRNA expression of TNF-alpha, IFN-gamma, and perforin in the muscles. Our results suggest that CX3CL1-
CX3CR1
interaction plays an important role in inflammatory cell migration into the muscle tissue of EAM mice. The results also point to the potential therapeutic usefulness of CX3CL1 inhibition and/or blockade of CX3CL1-
CX3CR1
interaction in idiopathic inflammatory myopathy.
...
PMID:Inhibition of CX3CL1 (fractalkine) improves experimental autoimmune myositis in SJL/J mice. 1627 59
The chemokine fractalkine (CX3C chemokine ligand 1; CX3CL1) and its receptor
CX3CR1
are involved in the pathogenesis of several diseases, including inflammatory bowel diseases such as Crohn's disease and ulcerative colitis, rheumatoid arthritis, hepatitis,
myositis
, multiple sclerosis, renal ischemia, and atherosclerosis. There are no orally available agents that modulate the fractalkine/
CX3CR1
axis. [(3
S
,4
R
)-1-[2-Chloro-6-(trifluoromethyl)benzyl]-3-{[1-(cyclohex-1-en-1-ylmethyl)piperidin-4-yl]carbamoyl}-4-methylpyrrolidin-3-yl]acetic acid (2S)-hydroxy(phenyl)acetate (E6130) is an orally available highly selective modulator of
CX3CR1
that may be effective for treatment of inflammatory bowel disease. We found that E6130 inhibited the fractalkine-induced chemotaxis of human peripheral blood natural killer cells (IC
50
4.9 nM), most likely via E6130-induced down-regulation of
CX3CR1
on the cell surface. E6130 had agonistic activity via
CX3CR1
with respect to guanosine 5'-3-
O
-(thio)triphosphate binding in
CX3CR1
-expressing Chinese hamster ovary K1 (CHO-K1) membrane and had no antagonistic activity. Orally administered E6130 ameliorated several inflammatory bowel disease-related parameters in a murine CD4
+
CD45RB
high
T-cell-transfer colitis model and a murine oxazolone-induced colitis model. In the CD4
+
CD45RB
high
T-cell transfer model, E6130 inhibited the migration of
CX3CR1
+
immune cells and decreased the number of these cells in the gut mucosal membrane. These results suggest that E6130 is a promising therapeutic agent for treatment of inflammatory bowel disease.
...
PMID:E6130, a Novel CX3C Chemokine Receptor 1 (CX3CR1) Modulator, Attenuates Mucosal Inflammation and Reduces CX3CR1
+
Leukocyte Trafficking in Mice with Colitis. 2884 93
