Enhanced NF-κB activation and cellular function in macrophages lacking IκB kinase 1 (IKK1)

I kappa B kinase (IKK) complex plays a key regulatory role in macrophages for NF-kappa B activation during both innate and adaptive immune responses. Because IKK1(-/-) mice died at birth, we differentiated functional macrophages from embryonic day 15.5 IKK1 mutant embryonic liver. The embryonic liver-derived macrophage (ELDM) showed enhanced phagocytotic clearance of bacteria, more efficient antigen-presenting capacity, elevated secretion of several key proinflarnmatory cytokines and chemokines, and known NF kappa B target genes. Increased NF kappa b activity in IKK1 mutant ELDM was the result of prolonged degradation of I kappa B alpha in response to infectious pathogens. The delayed restoration of I kappa B alpha in pathogen-activated IKK1(-/-) ELDM was a direct consequence of uncontrolled IKK2 kinase activity. We hypothesize that IKK1 plays a checkpoint role in the proper control of I kappa B alpha kinase activity in innate and adaptive immunity.