Molecular basis of age-associated cytokine dysregulation in LPS-stimulated macrophages

• DOI: 10.1189/jlb.0106024
• Publication Date: 2006-04-08T00:26:47Z
• Authors: R Lakshman Chelva...; Yushu Liu; Diana Popa; Marilyn L Getchell; Thomas V Getchell; Arnold J Stromberg; Subbarao Bondada
• Keywords: Immune Dysregulation

Aged humans and rodents are susceptible to infection with Streptococcus pneumoniae bacteria as a result of an inability make antibodies capsular polysaccharides. This is partly decreased production proinflammatory cytokines increased interleukin (IL)-10 by macrophages (Mphi) from aged mice. To understand the molecular basis cytokine dysregulation in mouse Mphi, microarray analysis was performed on RNA resting lipopolysaccharide (LPS)-stimulated Mphi control mice using Affymetrix Mouse Genome 430 2.0 gene chip. Two-way ANOVA demonstrated that at overall P < 0.01 level, 853 genes were regulated LPS (169 only young, 184 aged, 500 both). Expression systematic explorer revealed immune response (proinflammatory chemokines, cytokines, their receptors) signal transduction specifically reduced Mphi. Accordingly, expression Il1 Il6 reduced, Il10 increased, confirming our previous results. There also interferon-gamma. Genes Toll-like receptor-signaling pathway leading nuclear factor-kappaB activation down-regulated but IL-1 receptor-associated kinase 3, negative regulator this pathway, An increase for p38 mitogen-activated protein (MAPK) observed corresponding enzyme activity confirmed Western blotting. Low doses MAPK inhibitor (SB203580) enhanced IL-10 levels, indicating has role