IKKα in the regulation of inflammation and adaptive immunity

Inflammation is a beneficial response to insult or injury which plays an important role in orchestrating the adaptive immune response. The resolution of acute inflammation is an active process that involves the release of anti-inflammatory mediators and the termination of pro-inflammatory signalling pathways coincident with leucocyte apoptosis and phagocytic clearance and the migration of antigen-presenting cells from the site of inflammation to the local lymphatic tissue. The latter process is required for the development of adaptive immunity and immunological memory. The NF-κB (nuclear factor κB) pathway is an important regulator of inflammation and immunity; NF-κB activation is controlled by IKK [IκB (inhibitor of NF-κB) kinase] complex, which regulates NF-κB activation in response to pro-inflammatory stimuli. The IKK complex has two catalytic subunits, IKKα and IKKβ; recent research shows that these highly homologous kinases have distinct roles in inflammation and adaptive immunity. Here, we discuss the emerging roles for IKKα in the tight regulation of inflammation and the development of adaptive immune responses. Resolution of inflammation The inflammatory response requires co-ordinated activation of various signalling pathways that regulate the expression of pro-inflammatory mediators and recruitment of leucocytes; inflammation also has an important role in priming the adaptive immune response to generate immunological memory. Deregulation of this complex pathophysiological process may lead to chronic inflammation or inappropriate priming of adaptive immunity and autoimmune disease [1,2]. The NF-κB (nuclear factor κB) pathway has been strongly implicated in the pathogenesis of both chronic inflammatory diseases and autoimmune disease. NF-κB appears to play a pleiotropic role in immune and inflammatory responses; however, the recent description of a second, evolutionarily conserved, NF-κB pathway has revealed new insights into the regulation of NF-κB activation and the role of this pathway in innate and adaptive immunity. NF-κB NF-κB is a generic term for a family of transcription factors that play pivotal roles in inflammation and immunity [3], NF-κB consists of various dimers of Rel family proteins; RelA, c-Rel (the product of the cellular homologue of the avian-reticuloendotheliosis-virus transforming gene), RelB, p50 and p52 (expressed as precursor p105 and p100 respectively). Recent research has uncovered two separate pathways for NF-κB activation: the ‘canonical’ pathway is triggered