IL 1b driven neutrophilia preserves antibacterial defense in the absence of the kinase IKKb英文文献.pdfVIP

A rt i c l e s IL-1-driven neutrophilia preserves antibacterial defense in the absence of the kinase IKKb 1,2,9 2,3,8,9 4 5 1 1 2 Li-Chung Hsu , Thomas Enzler , Jun Seita , Anjuli M Timmer , Chih-Yuan Lee , Ting-Yu Lai , Guann-Yi Yu , 6 2 8 8 5,7 4 Liang-Chuan Lai , Vladislav Temkin , Ursula Sinzig , Thiha Aung , Victor Nizet , Irving L Weissman Michael Karin2 . d Transcription factor NF-kB and its activating kinase IKKb are associated with inflammation and are believed to be critical e v for innate immunity. Despite the likelihood of immune suppression, pharmacological blockade of IKK b–NF-kB has been r e considered as a therapeutic strategy. However, we found neutrophilia in mice with inducible deletion of IKK b ( IkkbD mice). s e r These mice had hyperproliferative granulocyte-macrophage progenitors and pregranulocytes and a prolonged lifespan of mature s t neutrophils that correlated with the induction of genes encoding prosurvival molecules. Deletion of interleukin 1 receptor 1 h g (IL-1R1) in IkkbD mice normalized blood cellularity and prevented neutrophil-driven inflammation. However, IkkbD Il1r1−/− i r mice, unlike IkkbD mice, were highly susceptible to bacterial infection, which indicated that signaling via IKK b–NF-kB l l A or IL-1R1 can maintain antimicrobial defenses in each other’s absence, whereas inactivation of both pathways severely . compromises innate immunity. c n I , a Neutrophils are phagocytic cells that provide a critical first line A key role in inflammation is served by th