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The transcription factor nuclear factor kappaB (NF-kappaB) is well known for its antiapoptotic action. However, in some disorders, such as cerebral ischemia, a proapoptotic function of NF-kappaB has been demonstrated. To analyze which subunit of NF-kappaB is functional in cerebral ischemia, we induced focal cerebral ischemia in mice with a germline deletion(More)
Inflammatory diseases at epithelial borders develop from aberrant interactions between resident cells of the tissue and invading immunocytes. Here, we unraveled basic functions of epithelial cells and immune cells and the sequence of their interactions in an inflammatory skin disease. Ubiquitous deficiency of the IkappaBalpha protein (Ikba(Delta)(/Delta))(More)
IKKbeta-dependent NF-kappaB activation plays a key role in innate immunity and inflammation, and inhibition of IKKbeta has been considered as a likely anti-inflammatory therapy. Surprisingly, however, mice with a targeted IKKbeta deletion in myeloid cells are more susceptible to endotoxin-induced shock than control mice. Increased endotoxin susceptibility(More)
Activation of the transcription factor NF-kappaB/Rel has been shown to be involved in inflammatory disease. Here we studied the role of RelA/p65, the main transactivating subunit, during acute pancreatitis using a Cre-loxP strategy. Selective truncation of the rela gene in pancreatic exocrine cells led to both severe injury of the acinar cells and systemic(More)
Nuclear factor kappa B (NF-kappaB) is a key regulator of the immune response, but in almost the same manner it is involved in induction of inflammation, proliferation and regulation of apoptosis. In the central nervous system activated NF-kappaB plays a neuroprotective role. While in some neurodegenerative disorders the role of NF-kappaB is well(More)
BACKGROUND & AIMS Nuclear factor (NF) kappaB1, NF-kappaB2, and Bcl-3 encode for proteins of the NF-kappaB/Rel/IkappaB families, known as regulators of innate and adoptive immune responses. Targeted disruption of these genes showed essential roles in lymphoid organ development and organization. METHODS NF-kappaB1-, NF-kappaB2-, and Bcl-3-deficient mouse(More)
SUMMARY IKKb-dependent NF-kB activation plays a key role in innate immunity and inflammation, and inhibition of IKKb has been considered as a likely anti-inflammatory therapy. Surprisingly, however, mice with a targeted IKKb deletion in myeloid cells are more susceptible to endo-toxin-induced shock than control mice. Increased endotoxin susceptibility is(More)
BACKGROUND & AIMS The transcription factor nuclear factor (NF)-kappaB plays a critical role in mediating survival of hepatocytes in response to tumor necrosis factor (TNF)-alpha during development because mice deficient for the NF-kappaB subunit RelA/p65 die in utero because of TNF-induced liver apoptosis. For the adult liver, conflicting concepts exist as(More)
Two major nuclear factor-kappaB (NF-kappaB) signalling pathways are involved in the regulation of the immune response. While the classical NF-kappaB pathway is responsible for regulation of genes encoding components of the innate immune response, the alternative NF-kappaB signalling pathway mediates processes of the adaptive immune system. To evaluate the(More)
Development of NKT cells was shown to depend on lymphotoxin (LT) and IL-15 signaling pathways as well as on cytokine receptor common gamma chain. After positive selection, NKT-cell precursors transit through progressive maturation stages including proliferative expansion within the NK1.1(-) window. The transcription factors that integrate different(More)