RESUMEN
BackgroundThe pro-inflammatory consequences of IL1ß expression contribute to the pathogenesis of bronchopulmonary dysplasia. Selectively targeting Lipopolysaccharide (LPS)-induced IκBß/NFκB signaling attenuates IL1ß mRNA expression in macrophages. Whether targeting IκBß/NFκB signaling affects the anti-apoptotic gene expression, a known consequence of global LPS-induced NFκB inhibition, is unknown.MethodsMacrophages (RAW 264.7, bone marrow-derived macrophage) were assessed for LPS-induced IL1ß mRNA/protein expression, anti-apoptotic gene expression, cell viability (trypan blue exclusion), and activation of apoptosis (caspase-3 and PARP cleavage) following pharmacologic and genetic attenuation of IκBß/NFκB signaling. Expressions of IL1ß and anti-apoptotic genes were assessed in endotoxemic newborn mice (P0) with intact (WT), absent (IκBß KO), and attenuated (IκBß overexpressing) IκBß/NFκB signaling.ResultsIn cultured macrophages, pharmacologic and genetic inhibition of LPS-induced IκBß/NFκB signaling significantly attenuated IL1ß mRNA and protein expression. Importantly, targeting IκBß/NFκB signaling did not attenuate LPS-induced expression of anti-apoptotic genes or result in cell death. In endotoxemic neonatal mice, targeting LPS-induced IκBß/NFκB signaling significantly attenuated pulmonary IL1ß expression without affecting the anti-apoptotic gene expression.ConclusionTargeting IκBß/NFκB signaling prevents LPS-induced IL1ß expression without inducing apoptosis in cultured macrophages and in the lungs of endotoxemic newborn mice. Inhibiting this pathway may prevent inflammatory injury without affecting the protective role of NFκB activity in the developing lung.