Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

0

ATF3 is a novel regulator of mouse neutrophil migration.


ABSTRACT: Expression of the activating transcription factor 3 (ATF3) gene is induced by Toll-like receptor (TLR) signaling. In turn, ATF3 protein inhibits the expression of various TLR-driven pro-inflammatory genes. Given its counter-regulatory role in diverse innate immune responses, we defined the effects of ATF3 on neutrophilic airway inflammation in mice. ATF3 deletion was associated with increased lipopolysaccharide (LPS)-driven airway epithelia production of CXCL1, but not CXCL2, findings concordant with a consensus ATF3-binding site identified solely in the Cxcl1 promoter. Unexpectedly, ATF3-deficient mice did not exhibit increased airway neutrophilia after LPS challenge. Bone marrow chimeras revealed a specific reduction in ATF3-/- neutrophil recruitment to wild type lungs. In vitro, ATF3-/- neutrophils exhibited a profound chemotaxis defect. Global gene expression analysis identified ablated Tiam2 expression in ATF3-/- neutrophils. TIAM2 regulates cellular motility by activating Rac1-mediated focal adhesion disassembly. Notably, ATF3-/- and ATF3-sufficient TIAM2 knockdown neutrophils, both lacking TIAM2, exhibited increased focal complex area, along with excessive CD11b-mediated F-actin polymerization. Together, our data describe a dichotomous role for ATF3-mediated regulation of neutrophilic responses: inhibition of neutrophil chemokine production, but promotion of neutrophil chemotaxis. Ly6G+ neutrophils were purified by magnetic beads from WT or ATF3 KO bone marrow and RNA was immediately isolated for global gene expression using microarrays.

ORGANISM(S): Mus musculus

SUBMITTER: Christopher Karp 

PROVIDER: E-GEOD-53973 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

Similar Datasets

2014-04-05 | GSE53973 | GEO
2024-07-29 | GSE234287 | GEO
2010-07-14 | E-GEOD-22925 | biostudies-arrayexpress
2022-07-22 | PXD035125 | Pride
2022-11-23 | GSE202873 | GEO
2022-08-20 | PXD035577 | Pride
2013-01-31 | E-GEOD-43890 | biostudies-arrayexpress
2020-03-04 | GSE146306 | GEO
2013-01-31 | E-GEOD-43889 | biostudies-arrayexpress
2007-10-02 | E-GEOD-2322 | biostudies-arrayexpress