biostudies-literatureUnknown5(12)Kim EY<h4>Background</h4>Activating transcription factor 3 (ATF3) is a negative regulator of proinflammatory cytokine expression in macrophages, and ATF3 deficient mice are more susceptible to endotoxic shock. This study addresses the role of ATF3 in the Kdo(2)-Lipid A-induced Toll-like receptor 4 (TLR4) signaling pathway in mouse embryonic fibroblasts (MEF). Kdo(2)-Lipid A upregulates ATF3 expression in wild type MEF cells and induces both nuclear factor kappa B (NF-κB) and c-Jun N-terminal kinase (JNK) activation via the TLR4 signaling pathway, while neither of these pathways is activated in ATF3-/- MEF cells. Interestingly, in contrast to Kdo(2)-Lipid A, the activation of both NF-κB and JNK by TNF-α was normal in ATF3-/- MEF cells.<h4>Methodology/principal findings</h4>We found that several gPloS onee14181https://www.ebi.ac.uk/biostudies/studies/S-EPMC2996292biostudies-literatureATF3 plays a key role in Kdo2-lipid A-induced TLR4-dependent gene expression via NF-κB activation.PMC2996292Kim EYShin HYChoi YMChoi SKim DGKim JYRhee DKKwon HKKim YSfalseATF3 plays a key role in Kdo2-lipid A-induced TLR4-dependent gene expression via NF-κB activation.<h4>Background</h4>Activating transcription factor 3 (ATF3) is a negative regulator of proinflammatory cytokine expression in macrophages, and ATF3 deficient mice are more susceptible to endotoxic shock. This study addresses the role of ATF3 in the Kdo(2)-Lipid A-induced Toll-like receptor 4 (TLR4) signaling pathway in mouse embryonic fibroblasts (MEF). Kdo(2)-Lipid A upregulates ATF3 expression in wild type MEF cells and induces both nuclear factor kappa B (NF-κB) and c-Jun N-terminal kinase (JNK) activation via the TLR4 signaling pathway, while neither of these pathways is activated in ATF3-/- MEF cells. Interestingly, in contrast to Kdo(2)-Lipid A, the activation of both NF-κB and JNK by TNF-α was normal in ATF3-/- MEF cells.<h4>Methodology/principal findings</h4>We found that several g2010-01-01T00:00:00Z2010 Dec2025-04-04T21:04:44.413Z2019-03-26T23:09:10ZS-EPMC29962922115203910.1371/journal.pone.0014181