RelB Is Differentially Regulated by IκB Kinase-α in B Cells and Mouse Lung by Cigarette Smoke

• DOI: 10.1165/rcmb.2008-0207oc
• Publication Date: 2008-08-08T01:50:02Z
• Authors: Se-Ran Yang; Hongwei Yao; Saravanan Rajendr...; Sangwoon Chung; Indika Edirisinghe; Samantha Valvo; George Fromm; Michael J. McCabe; Patricia J. Sime; Richard P. Phipps; Jian-Dong Li; Michael Bulger; Irfan Rahman
• Keywords: RELB; Proinflammatory cytokine

The activation of transcription factor NF-kappaB is controlled by two main pathways: the classical canonical (RelA/p65-p50)- and alternative noncanonical (RelB/p52)-NF-kappaB pathways. RelB has been shown to play a protective role in RelA/p65-mediated proinflammatory cytokine release immune-inflammatory lymphoid cells. Increased infiltration macrophages cells occurs lungs patients with chronic obstructive pulmonary disease, leading abnormal inflammation. We hypothesized that RelB, its signaling pathway, differentially regulated B lung cells, differential regulation cytokines response cigarette smoke (CS). CS exposure increased levels NF-kappaB-inducing kinase associated recruitment on promoters IL-6 macrophage inflammatory protein-2 genes mouse lung. Treatment cell line, MonoMac6, extract showed RelB. In contrast, was degraded proteasome-dependent mechanism lymphocytes (human Ramos, WEHI-231, primary spleen cells), suggesting exposure. Transient transfection dominant negative IkappaB-kinase-alpha double mutants partially attenuated extract-mediated loss normalized level macrophages. Taken together, these data suggest macrophages, IkappaB-kinase-alpha-dependent mechanism. Rapid degradation signals for RelA/p65 ability suppress