IKK?-I-?B?-c-Rel/p50: a new axis of NF-?B activation in lung epithelial cells.

ABSTRACT: Cigarette smoke (CS), a major risk factor for developing lung cancer, is known to activate transcriptional activator nuclear factor kappa B (NF-?B). However, the underlying mechanism of this activation remains unclear because of conflicting reports. As NF-?B has a pivotal role in the generation and maintenance of malignancies, efforts were targeted towards understanding its activation mechanism using both ex vivo and in vivo studies. The results show that CS-induced NF-?B activation mechanism is different from that of other pro-inflammatory signals such as lipopolysaccharide (LPS). The NF-?B dimer that translocates to the nucleus upon stimulation with CS is predominantly composed of c-Rel/p50 and this translocation involves degradation of I-?B? and not I-?B?. This degradation of I-?B? depends on IKK? activity, which preferentially targets I-?B?. Consistently, CS-activated form of IKK? was found to be different from that involved in LPS activation as neither Ser177 nor Ser181 of IKK? is crucial for CS-induced NF-?B activation. Thus, unlike other pro-inflammatory stimulations where p65 and I-?B? have a central role, the predominantly active signaling cascade in CS-induced NF-?B activation in the lung epithelial cells comprises of IKK?-I-?B?-c-Rel/p50. Thus, this study uncovers a new axis of NF-?B activation wherein I-?B? and c-Rel have the central role.

SUBMITTER: Maity PC 

PROVIDER: S-EPMC3412642 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature