Age-related activation of MKK/p38/NF-κB signaling pathway in lung: From mouse to human

摘要: Abstract We and others previously reported that the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) IL-6 significantly accumulate with age in mouse lung. This is accompanied by elevated phosphorylation of p38. Here, we further investigate whether aging affects activation p38 signaling inflammatory reaction after exposure to lipopolysaccharide (LPS) lungs mice vivo humans ex vivo. The data showed peaked at 0.5 h then rapidly declined young (2-month-old) lung, intranasal inhalation challenge LPS. In contract, 24 h was sustained longer aged (20-month-old) mice. As well as altered p38, activations its upstream activator MKK downstream substrate NF-κB were also changed mice, which corresponded absence early phase but delayed increases concentrations TNF-α, IL-1β IL-6. Consistent above observations similar patterns occurred human lungs. Compared younger from adult–middle subjects, NF-κB, production cytokines increased older subjects Exposure lung cells LPS induced rapid these not cytokines. LPS-induced 0.25 h exposure, declined. did induce marked changes phase, either or subjects. contrast, relatively late, 16 h These support hypothesis pathway baseline response elderly may play important roles susceptibility injury.