Acute lung injury occurs as a result of a cascade of cellular events initiated by either infectious or noninfectious inflammatory stimuli. An elevated level of proinflammatory mediators combined with a decreased expression of anti-inflammatory molecules is a critical component of lung inflammation. Expression of proinflammatory genes is regulated by transcriptional mechanisms. Nuclear factor-ka...

Nuclear factor kappa B (NF-kappa B) is a transcription factor that regulates expression of several genes coding for inflammatory and immunoregulatory proteins including the neutrophil chemotactic cytokine MIP-2. In previous studies we found that crocidolite asbestos activates the nuclear translocation of NF-kappa B as well as MIP-2 gene expression in rat alveolar type II cells. Here we report t...

Natural killer T (NKT) cells have been implicated in diverse immune responses ranging from suppression of autoimmunity to tumor rejection. Thymus-dependent NKT cells are positively selected by the major histocompatibility complex class I-like molecule CD1d, but the molecular events downstream of CD1d are still poorly understood. Here, we show that distinct members of the Rel/nuclear factor (NF)...

NF-kappa B has been implicated in the survival and differentiation of PC12 cells. In this study, we examined the effect of the NF-kappa B-inducing kinase (NIK) on these processes. When inducibly expressed in PC12 cells, a kinase-proficient but not -deficient form of NIK promoted neurite process formation and mediated anti-apoptotic signaling. As expected, NIK expression led to I kappa B kinase ...

To determine the role of respiratory epithelial cells in the inflammatory response to inhaled endotoxin, we selectively inhibited NF-kappa B activation in the respiratory epithelium using a mutant I kappa B-alpha construct that functioned as a dominant negative inhibitor of NF-kappa B translocation (dnI kappa B-alpha). We developed two lines of transgenic mice in which expression of dnI kappa B...

Although immunoglobulin (Ig)M(hi)IgD(lo/-)CD21(hi) marginal zone B cells represent a significant proportion of naive peripheral splenic B lymphocytes, few of the genes that regulate their development have been identified. This subset of peripheral B cells fails to emerge in mice that lack nuclear factor (NF)-kappa Bp50. Less drastic reductions in marginal zone B cell numbers are also seen in th...

The molecular circuitry underlying innate immunity is constructed of multiple, evolutionarily conserved signaling modules with distinct regulatory targets. The MAP kinases and the IKK-NF-kappa B molecules play important roles in the initiation of immune effector responses. We have found that the Drosophila NF-kappa B protein Relish plays a crucial role in limiting the duration of JNK activation...

Preeclampsia affects 7-10% of all pregnancies, and is a major cause of maternal and fetal morbidity and mortality. Although enhanced apoptosis is well known in placentas with preeclampsia, the role of transcription factor nuclear factor-kappa B (NF-kappa B) in the process is still being debated. In this work, we investigate the relationship between NF-kappa B expression and trophoblastic cell a...