RACK-1 expression and cytokine production in leukocytes obtained from AD patients

Aging Clinical and Experimental Research - Tập 18 - Trang 153-157 - 2013
Marco Racchi1, Elena Sinforiani2, Stefano Govoni1, Marina Marinovich3, Corrado L. Galli3, Emanuela Corsini3
1Department of Experimental and Applied Pharmacology, University of Pavia, Italy
2IRCCS C, Mondino, Pavia
3Laboratory of Toxicology, Department of Pharmacological Sciences, University of Milano, Milano, Italy

Tóm tắt

Background and aims: The purpose of this study was to evaluate in vitro cytokine production in blood leukocytes obtained from sporadic AD patients, aged controls and young individuals. Methods: Diluted whole blood was treated in the presence or absence of LPS (1 μg/mL) for varying times (3–48 h). The release of IL-8, IL-10 and TNF-α in conditioned media was evaluated by commercially available sandwich ELISA. Results: Data obtained are indicative of the presence of an unregulated systemic inflammation in AD patients. Leukocytes obtained from AD patients had increased spontaneous TNF-α release and decreased LPS-induced IL-10 production, in comparison with both old controls and young subjects, while identical IL-8 production was observed in all groups. The last finding indicates that there was no shift in the potency or efficacy of the response towards LPS with aging, but alterations in downstream signal transduction pathways are probably altered with aging and pathological conditions. Conclusions: The dysregulation of cytokine production observed in AD patients may partially be explained by a significant reduction in the expression of RACK-1, a protein crucial for integration of signaling pathways with different physiological functions, such as cytokine production.

Tài liệu tham khảo

Bruunsgaard H, Pedersen AN, Pedersen BK. Aging and proinflammatory cytokines. Curr Opin Hematol 2001; 8: 131–6. Lio D, Scola L, Crivello A, et al. Inflammation, genetics, and longevity: further studies on the protective effects in men of IL-10 — 1082 promoter SNP and its interaction with TNF-α -308 promoter SNP. J Med Genet 2003; 40: 296–9. Corsini E, Battaini F, Lucchi L, et al. A defective protein kinase C anchoring system underlying age-associated impairment in TNF-ga production in rat macrophages. J Immunol 1999; 163: 3468–73. Corsini E, Racchi M, Sinforiani E, et al. Age-related decline in RACK-1 expression in human leukocytes is correlated to plasma levels of dehydroepiandrosterone. J Leukocyte Biol 2005; 77: 247–56. Corsini E, Lucchi L, Meroni M, et al. In vivo dehy-droepiandrosterone restores age-associated defects in protein kinase C signal transduction pathway and related functional responses. J Immunol 2002; 168: 1753–8. Viviani B, Bartesaghi S, Corsini E, Galli CL, Marinovich M. Cytokines role in neurodegenerative events. Toxicol Lett 2004; 149: 85–9. Hanada T, Yoshimura A. Regulation of cytokine signaling and inflammation. Cytokine Growth Factor Rev 2002; 13: 413–21. Bruunsgaard H, Pedersen AN, Schroll M, Skinhoi P, Pedersen BK. Impaired production of proinflammatory cytokines in response to lipopolysaccharide (LPS) stimulation in elderly human. Clin Exp Immunol 1999; 118: 235–41. Gleckman R, Hibert D. Afebrile bacteremia. A phenomenon in geriatric patients. JAMA 1982; 248: 1478–81.