Overexpressed nuclear factor κB correlates with enhanced expression of interleukin-1β and inducible nitric oxide synthase in aged murine lungs to endotoxic stress

Background Transcriptional regulation is a major determinant of interleukin-1β (IL-1β) protein synthesis. Nuclear factor κB (NF-κB) plays a central role in the regulation of IL-1β and subsequent IL-1β-dependent inflammatory processes. Previously, we observed in a murine endotoxic stress model a progressive increase with age in the amount of IL-1β mRNA. We test the aging pulmonary response of NF-κB and NF-κB-dependent genes, IL-1β, and inducible nitric oxide synthase (iNOS) in the same model. Methods Young (2-month-old) and senescent (25-month-old) mice were given 0.5 mg/kg lipopolysaccharide (LPS) intraperitoneally. Lung and blood samples were harvested after 4 hours. IL-1β production in blood samples and the expression levels of protein and mRNA of IL-1β and iNOS in lung tissues were measured. NF-κB binding activity in lung tissues was also determined. Results LPS induced higher levels of IL-1β in the sera and lungs of senescent mice over young mice. Northern and Western blot analyses showed that mRNA and protein signals of IL-1β and iNOS were significantly higher in old lungs than in young lungs. Electrophoretic mobility shift assay also showed that NF-κB activation was significantly higher in the older animals. Conclusions Our results suggest that elevated activation of NF-κB, at least in part, contributes to the dysregulated expression of IL-1β and iNOS in the lungs of senescent animals. Thus increased expression of proinflammatory cytokines and inflammatory responsive genes in the lung may play a role in the increased susceptibility in aging animals to endotoxic stress.