PMID- 18054398 OWN - NLM STAT- MEDLINE DCOM- 20080519 LR - 20220310 IS - 0166-4328 (Print) IS - 0166-4328 (Linking) VI - 188 IP - 1 DP - 2008 Mar 17 TI - Gene expression profiling reveals upregulation of Tlr4 receptors in Cckb receptor deficient mice. PG - 62-70 AB - 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. FAU - Koks, Sulev AU - Koks S AD - Department of Physiology, Centre of Molecular and Clinical Medicine, University of Tartu, Tartu 50411, Estonia. Sulev.Koks@ut.ee FAU - Fernandes, Cathy AU - Fernandes C FAU - Kurrikoff, Kaido AU - Kurrikoff K FAU - Vasar, Eero AU - Vasar E FAU - Schalkwyk, Leonard C AU - Schalkwyk LC LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20071026 PL - Netherlands TA - Behav Brain Res JT - Behavioural brain research JID - 8004872 RN - 0 (Receptor, Cholecystokinin B) RN - 0 (Toll-Like Receptor 4) RN - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases) SB - IM MH - Analysis of Variance MH - Animals MH - Disease Models, Animal MH - Gene Expression Profiling MH - Ligation MH - Lumbar Vertebrae MH - Male MH - Medulla Oblongata/immunology/metabolism MH - Mesencephalon/immunology/metabolism MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Mitogen-Activated Protein Kinase Kinases/*metabolism MH - Pain Threshold/*physiology MH - Receptor, Cholecystokinin B/genetics/*physiology MH - Sciatic Neuropathy/immunology/*metabolism MH - Signal Transduction MH - Spinal Cord/immunology/metabolism MH - Toll-Like Receptor 4/*metabolism MH - Up-Regulation EDAT- 2007/12/07 09:00 MHDA- 2008/05/20 09:00 CRDT- 2007/12/07 09:00 PHST- 2007/08/21 00:00 [received] PHST- 2007/10/17 00:00 [revised] PHST- 2007/10/21 00:00 [accepted] PHST- 2007/12/07 09:00 [pubmed] PHST- 2008/05/20 09:00 [medline] PHST- 2007/12/07 09:00 [entrez] AID - S0166-4328(07)00561-X [pii] AID - 10.1016/j.bbr.2007.10.020 [doi] PST - ppublish SO - Behav Brain Res. 2008 Mar 17;188(1):62-70. doi: 10.1016/j.bbr.2007.10.020. Epub 2007 Oct 26.