BioProject

Despite much progress, the specific role of some the putative intracellular signaling players upstream to inflammatory gene expression activated by Toll-like receptor (TLRs) in the immune response remains unknown. More...

Despite much progress, the specific role of some the putative intracellular signaling players upstream to inflammatory gene expression activated by Toll-like receptor (TLRs) in the immune response remains unknown. For instance, the TLR-inducible Ras guanine exchange factor member 1b (RasGEF1b) was previously shown to be expressed in activated macrophages, but its specific function is still obscure. To investigate the role of RasGEF1b in TLR-mediated innate immune response, we generated Rasgef1bfl/fl mice for tissue conditional gene deletion . We found that the expression and production of the neutrophil chemoattractant chemokine KC/Cxcl1 was impaired in response to TLRs stimulation of bone marrow derived macrophages (BMDMs) devoid of RasGEF1b. The production of KC/Cxcl1 was also impaired in in vivo models of LPS-induced peritonitis, and R848-induced acute lung injury inflammation. RasGEF1b was not required or sufficient to neither induce nor increase the transcriptional activation of Cxcl1 promoter. In addition, TLR-triggered inflammatory activation of NF-ΚB signaling pathway was unimpaired in macrophages lacking RasGEF1b suggesting a mechanism independent of the NF-B transcription factor. Our data presented herein revealed an important role of RasGEF1b in innate immunity by regulating gene expression, following TLR stimulation. Overall design: Bone marrow derived macrophages (BMDMs) were collected from wild type and Rasgef1b_fl/fl_vav-icre mice, and were stimulated or not with R848. Transcriptome analysis was performed using a Mouse Genome 2.1 ST Array Strip (Affymetrix). Less...