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CCR9C-C Chemokine Receptor 9 (gene)
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In the case of T cells, the antigen presented by mucosal dendritic (CD103+) cells leads to the upregulation of CCR9 and the adhesion molecule [alpha]4[beta]7 which binds MALT-expressed mucosal vascular addressin cell adhesion molecule 1 (MADCAM1).
[59] investigated the possible regulative role of Notchl in the expression and function of chemokine receptors CCR5, CCR9, and CXCR4 that play a role in determining blast malignant properties and localization of extramedullary infiltrations in leukemia.
GlaxoSmithKline previously exercised its option to license ChemoCentryx's CCX282-B (Traficet-EN), now designated GSK1605786 (also called GSK'786), an orally active CCR9 inhibitor, for the treatment of inflammatory bowel disease, in January 2010.
In experimental studies it has been shown that 1,25[(OH).sub.2]D suppressed gut hormone receptors [alpha]4[beta]7, an integrin adhesion molecule expressed by most leukocytes, and chemokine receptor 9 (CCR9), a highly specific receptor expressed by T-cells that migrate selectively to the digestive tract.
ChemoCentryx's lead compound, Traficet-EN, a specific CCR9 antagonist, is currently in a multi-national clinical trial, called PROTECT-1, in patients with moderate-to-severe Crohn's disease.
p-53-dependent benzene-induced decrease or increase Decrease Adcy6, ApoE, AQ1, B cell antigen receptor, Cam III, CCR9, E2F1, WT: decreased FATP4, Fscn1, GPCR (EB11), Ig kappa light chain, IgA, IgH, p53-KO: unchanged mur42, Pdk1, PPT-B, Prkm1, TP, TRBF1 Increase Adipose fatty acid binding protein, Adh-3, caspase-11, cyclin G1, WT: increased CYP7B1, EGFB-3, emp-1, FKBP23, c-fos, Hox-4.9, Int-1, Lfc, p53-KO: unchanged Krtl-12, mLimk1, MDC2, Mtcp1, Nr2b1, p58 (PKI), Pcnt, PFK, Pkacb, PGII, PTG, beta- spectrin, SPI-3, SNK, TSC-2 C.
Then, RA signaling via the RARa receptor regulates the transcription of the promoter regions of the a4 gene subunit of [alpha]4[beta]7 integrin and the CC chemokine receptor 9 (CCR9) gene on target cells [10], promoting the synthesis and expression of gut-trafficking receptors [alpha]4[beta]7 and CCR9 in the cellular membrane.