Transcriptomics

Dataset Information

59

Tpl2 promotes chemokine/chemokine receptor expression and macrophage migration during acute inflammation


ABSTRACT: 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. microarray was used to profile the genome-wide expression patterns in Tpl2 wild-type and deficient macrophage.

ORGANISM(S): Mus musculus  

SUBMITTER: Lisa A Mielke   Sean M Rowley  Wendy T Watford  Lai Wei 

PROVIDER: E-GEOD-48338 | ArrayExpress | 2014-06-03

SECONDARY ACCESSION(S): GSE48338PRJNA209719

REPOSITORIES: GEO, ArrayExpress

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Publications

Tumor progression locus 2 (Tpl2) kinase promotes chemokine receptor expression and macrophage migration during acute inflammation.

Rowley Sean M SM   Kuriakose Teneema T   Dockery Lee M LM   Tran-Ngyuen Thi T   Gingerich Aaron D AD   Wei Lai L   Watford Wendy T WT  

The Journal of biological chemistry 20140408 22


In autoimmune diseases, the accumulation of activated leukocytes correlates with inflammation and disease progression, and, therefore, the disruption of leukocyte trafficking is an active area of research. The serine/threonine protein kinase Tpl2 (MAP3K8) regulates leukocyte inflammatory responses and is also being investigated for therapeutic inhibition during autoimmunity. Here we addressed the contribution of Tpl2 to the regulation of macrophage chemokine receptor expression and migration in  ...[more]

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