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Gene expression profiling reveals upregulation of Tlr4 receptors in Cckb receptor deficient mice

Kõks, Sulev and Fernandes, Cathy and Kurrikoff, Kaido and Vasar, Eero and Schalkwyk, Leonard C (2008) 'Gene expression profiling reveals upregulation of Tlr4 receptors in Cckb receptor deficient mice.' Behavioural Brain Research, 188 (1). pp. 62-70. ISSN 0166-4328

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The cholecystokinin B (2) receptor knockout (Cckbr KO) protects against allodynia induced by chronic constriction injury (CCI). The mechanism of this phenomenon is unknown, but must involve persistent changes in pain modulation and/or inflammatory pathways. We performed a gene expression study in two brain areas (midbrain and medulla) after surgical induction of CCI in Cckbr KO and wild-type (wt) control mice. The patterns of gene expression differences suggest that the immune system is activated in higher brain structures following CCI in the wt mice. The strongest differences include genes related to the MAPK pathway activation and cytokine production. In Cckbr KO mice this expressional pattern was absent. In addition, we found significant elevation of the Toll-like receptor 4 (Tlr4) in the supraspinal structures of the mice with deleted Cckbr compared to wt control mice. This up-regulation is most likely induced by the deletion of Cckbr. We suggest that there is a functional deficiency in the Tlr4 pathway which disables the development of neuropathic pain in Cckbr KO mice. Indeed, real time PCR analysis detected a CCI-induced upregulation of Tlr4 and Il1b expression in the lumbar region of wt but not Cckbr KO mice. Gene expression profiling indicates that elements of the immune response are not activated in Cckbr KO mice following CCI. Our findings suggest that there may be a role for CCK in the regulation of innate immunity. © 2007 Elsevier B.V. All rights reserved.

Item Type: Article
Uncontrolled Keywords: cholecystokinin B receptor; toll-like receptor 4; chronic constriction injury; gene expression profiling; microarrays
Subjects: Q Science > QH Natural history > QH426 Genetics
Divisions: Faculty of Science and Health
Faculty of Science and Health > Life Sciences, School of
SWORD Depositor: Elements
Depositing User: Elements
Date Deposited: 17 Dec 2014 18:55
Last Modified: 15 Jan 2022 00:42

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