Aging alters the production of iNOS, arginase and cytokines in murine macrophages

Cecilio, Carla Aparecida; Costa, Esther Da; Simioni, Patricia Ucelli; Gabriel, Dirce Lima; Tamashiro, Wirla Maria da Silva Cunha

doi:10.1590/s0100-879x2011007500067

Cited by 32 publications

(15 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Increased phosphorylation of eIF-2α is observed in different murine tissues during aging (Ladiges et al 2000 ;Segev et al 2013 ) middle-aged mice than in young mice ( Fig. This result agreed with previous fi ndings (Cecílio et al 2011 ). This result agreed with previous fi ndings (Cecílio et al 2011 ).…”

Section: Post-transcriptional Suppression Of Lps-stimulated Infl Ammasupporting

confidence: 92%

“…Subsequent activation of downstream intracellular signaling leads to the production of proinfl ammatory and bactericidal mediators, including tumor necrosis factor-α (TNFα), inducible nitric oxide synthase (iNOS), etc. LPS-stimulated iNOS production by macrophages is also impaired with advancing age (Cecílio et al 2011 ) (Fig. The infl ammatory responses of macrophages facilitate the accumulation and activation of immune cells in infectious foci and pathogen killing.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Physical Activity, Exercise, Sedentary Behavior and Health

Kanosue¹,

Oshima²,

Cao

et al. 2015

View full text Add to dashboard Cite

Section: Post-transcriptional Suppression Of Lps-stimulated Infl Ammasupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Physical Activity, Exercise, Sedentary Behavior and Health

Kanosue¹,

Oshima²,

Cao

et al. 2015

View full text Add to dashboard Cite

“…Previous studies found elevated pro-inflammatory factor levels with age [26]. High levels of TNF-α, iNOS, IL-1β, and IFN-γ have been observed when aged MΦ were challenged with IFN-γ or LPS [22, 27, 28]. These findings suggest that aged MΦ remain in a preactivated resting state that enhances their responsiveness to exposure of pro-inflammatory stimuli [29].…”

Section: Discussionmentioning

confidence: 87%

Aging Affects Bone Marrow Macrophage Polarization: Relevance to Bone Healing

Gibon

Loi

Córdova

et al. 2016

Regen. Eng. Transl. Med.

View full text Add to dashboard Cite

Macrophages are an important component of the inflammatory cascade by initiating and modulating the processes leading to tissue regeneration and bone healing. Depending on the local environment, macrophages can be polarized into M1 (pro-inflammatory) or M2 (anti-inflammatory) phenotypes. In order to assess the effects of aging on macrophage function, bone marrow macrophage polarization using primary bone marrow macrophages (BMMs) from young (8 weeks old) and aged (72 weeks old) wild-type male C57BL/6J mice was analyzed. Fluorescence-activated cell sorting (FACS) analysis (CD11b, iNOS, CD206), qRT-PCR (iNOS, TNF-α, CD206, Arginase 1), and ELISA (TNF-α, IL-1ra) were performed to compare the M1 and M2 phenotypic markers in young and aged mouse macrophages. Once M1 and M2 macrophage phenotypes were confirmed, the results showed that TNF-α mRNA was significantly upregulated in aged M1s after interferon gamma (INF-γ) exposure. Arginase 1 and CD206 mRNA expression were still upregulated with IL4 stimulation in aged macrophages, but to a lesser extend than those from younger animals. TNF-α secretion was also significantly increased in aged M1s compared to young M1s, following lipopolysaccharide (LPS) exposure. However, the IL-1ra secretion did not increase accordingly in aged mice. The results demonstrate that, compared to younger animals, aging of bone marrow derived macrophages increases the resting levels of oxidative stress, and the ratios of pro- to anti-inflammatory markers. These age-related changes in macrophage polarization may explain in part the attenuated response to adverse stimuli and delay in processes such as fracture healing seen in the elderly. Lay Summary Bone healing is a complex process that involves both biological and mechanical factors. Macrophages are key cells that regulate the events involved in bone healing, especially the initial inflammatory phase. In this biological cascade of events, macrophages present as different functional phenotypes including uncommitted (M0), pro-inflammatory (M1), and anti-inflammatory (M2), a process called macrophage polarization. A clear understanding of the effects of aging on macrophage polarization is critical to modulating adverse events such as fractures, atraumatic bone loss, and tissue regeneration in an aging population.

show abstract

“…Much of the literature describes aged macrophage hypersensitivity and increased responsiveness to inflammatory signals. For example, when aged BMDMs are challenged with IFNγ or LPS, they increase their expression of arginase and secrete characteristic pro-inflammatory M1 and Th1 cytokines, such as TNFα, NOS2, IL-1β, and IFNγ [ 30 , 37 , 39 ]. Moreover, aged macrophages increase their surface density of TLR4, the receptor for LPS, permitting a faster and enhanced inflammatory response [ 40 ].…”

Section: Aging and Macrophagesmentioning

confidence: 99%

Aging, inflammation, stem cells, and bone healing

2016

View full text Add to dashboard Cite

Complex interactions among cells of the monocyte-macrophage-osteoclast lineage and the mesenchymal stem cell-osteoblast lineage play a major role in the pathophysiology of bone healing. Whereas the former lineage directs inflammatory events and bone resorption, the latter represents a source of cells for bone regeneration and immune modulation. Both of these lineages are affected by increasing age, which is associated with higher baseline levels of inflammatory mediators, and a significant reduction in osteogenic capabilities. Given the above, fracture healing, osteoporosis, and other related events in the elderly present numerous challenges, which potentially could be aided by new therapeutic approaches to modulate both inflammation and bone regeneration.

show abstract

Aging alters the production of iNOS, arginase and cytokines in murine macrophages

Cited by 32 publications

References 38 publications

Physical Activity, Exercise, Sedentary Behavior and Health

Physical Activity, Exercise, Sedentary Behavior and Health

Aging Affects Bone Marrow Macrophage Polarization: Relevance to Bone Healing

Aging, inflammation, stem cells, and bone healing

Contact Info

Product

Resources

About