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Series GSE48338 Query DataSets for GSE48338
Status Public on Jun 03, 2014
Title Tpl2 promotes chemokine/chemokine receptor expression and macrophage migration during acute inflammation
Organism Mus musculus
Experiment type Expression profiling by array
Summary In autoimmune diseases, accumulation of activated leukocytes correlates with inflammation and disease progression, and therefore, disruption of leukocyte trafficking is an active area of research. The protein kinase Tpl2 (MAP3K8) regulates leukocyte inflammatory responses and is also being investigated for therapeutic inhibition during autoimmunity. Herein, we addressed the contribution of Tpl2 to the regulation of macrophage chemokine and chemokine receptor expression and subsequent migration in vivo using a mouse model of Tpl2 ablation. We found that gene expression of the chemokine ligands CCL2, CCL7, CXCL2, and CXCL3 as well as the chemokine receptors CCR1 and CCR5 were reduced in macrophages from the bone marrow and peritoneal cavities of tpl2-/- mice following stimulation with LPS. LPS stimulation repressed chemokine receptor expression of CCR1, CCR2 and CCR5. Notably, LPS-induced repression of CCR1 and CCR5 was significantly enhanced in Tpl2-deficient macrophages and was observed to be dependent upon Erk activation and independent of PI3K and mTOR signaling. Consistent with alterations in chemokine and chemokine receptor expression, tpl2-/- macrophages were defective in trafficking to the peritoneal cavity following thioglycollate-induced inflammation. Overall, this study demonstrates a Tpl2-dependent mechanism for macrophage expression of both chemokine receptors and their ligands and provides further insight into how Tpl2 inhibition may disrupt inflammatory networks in vivo.
 
Overall design microarray was used to profile the genome-wide expression patterns in Tpl2 wild-type and deficient macrophage.
 
Contributor(s) Rowley SM, Mielke LA, Wei L, Watford WT
Citation(s) 24713702
Submission date Jun 26, 2013
Last update date Feb 11, 2019
Contact name Lai Wei
E-mail(s) weil2@mail.nih.gov
Phone 3014961480
Organization name NIH/NEI/NCCAM
Street address 10 Center Dr. Room 2B47
City Bethesda
State/province MD
ZIP/Postal code 20892
Country USA
 
Platforms (1)
GPL1261 [Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array
Samples (8)
GSM1175312 BMDM, Tpl2 WT, unstimulated, biological replicate 1
GSM1175313 BMDM, Tpl2 WT, unstimulated, biological replicate 2
GSM1175314 BMDM, Tpl2 KO, unstimulated, biological replicate 1
Relations
BioProject PRJNA209719

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE48338_RAW.tar 50.3 Mb (http)(custom) TAR (of CEL)
Raw data provided as supplementary file
Processed data included within Sample table

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