Department of Medicine, Division of Infectious Diseases and Immunology
Interleukin-1beta; Macrophages; Carrier Proteins
Immunology and Infectious Disease
BACKGROUND: Cytokines regulated by the inflammasome pathway have been extensively implicated in various age-related immune pathologies. We set out to elucidate the contribution of the nod-like receptor protein 3 (NLRP3) inflammasome pathway to the previously described deficiencies in IL-1beta production by macrophages from aged mice. We examined the production of pro-IL-1beta and its conversion into IL-1beta as two separate steps and compared these cytokine responses in bone marrow derived macrophages from young (6-8 weeks) and aged (18-24 months) C57BL/6 mice.
FINDINGS: Relative to macrophages from young mice, macrophages from aged mice produced less pro-IL-1beta after TLR4 stimulation with LPS. However upon activation of the NLRP3 inflammasome with ATP, macrophages from young and aged mice were able to efficiently convert and secrete intracellular pro-cytokines as functional cytokines.
CONCLUSIONS: Lower levels of IL-1beta production are a result of slower and lower overall production of pro-IL-1beta in macrophages from aged mice.
Immunity and ageing : I and A
Ramirez, Alejandor; Rathinam, Vijay A. K.; Fitzgerald, Katherine A.; Golenbock, Douglas T.; and Mathew, Anuja, "Defective pro-IL-1beta responses in macrophages from aged mice" (2012). Open Access Articles. 2383.