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IL-1β-driven neutrophil biogenesis and survival preserve anti-bacterial defense in IKKβ deficiency

ABSTRACT: IKKβ-dependent NF-κB activation is associated with inflammation and tumorigenesis and is critical for innate immunity. Despite risk of immune suppression, pharmacological blockade of IKKβ/NF-κB has been considered as an attractive strategy for treatment of inflammatory diseases and cancer. Unexpectedly, treatment with IKKβ inhibitors caused neutrophilia, which also occurs in mice with inducible IKKβ deletion, termed IkkβΔ mice. IkkβΔ mice show hyperproliferation of granulocyte progenitors and increased neutrophil lifespan. Deletion of IL-1 receptor 1 in IkkβΔ mice restored normal blood cellularity and prevented neutrophil-driven inflammation. However, IkkβΔ/Il-1r1-/- mice, in contrast to IkkβΔ mice, are highly susceptible to bacterial infections indicating that either IKKβ/NF-κB or IL-1R signaling are sufficient for maintaining anti-microbial defenses, but inactivation of both pathways severely compromises innate immunity. Thioglycollate-elicited peritoneal neutrophils were purified from IkkβF/F and IkkβΔ mice using anti-Ly-6G magnetic beads and cultured. Ly-6G+ neutrophils were collected and total RNA was extracted with TRIzol® (Invitrogen) and was purified by RNA micro cleanup Kit (Qiagen). Biotinylated cRNA was synthesized using an RNA Amplification Kit (Ambion) following manufacturer's directions. Biotin-labeled cRNA was hybridized to Illumina Mouse-Ref8 BeadChips (Illumina) and the results were analyzed using BeadStudio v3.1 software. Data analysis and quality control were carried out using Partek® software.

ORGANISM(S): Mus musculus

SUBMITTER: Liang-Chuan Lai

PROVIDER: E-GEOD-25211 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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IL-1β-driven neutrophil biogenesis and survival preserve anti-bacterial defense in IKKβ deficiency

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