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

Cecílio, C.A.; Costa, E.H.; Simioni, Patricia Ucelli; Gabriel, D.L.; Tamashiro, W.M.S.C.

doi:10.1590/s0100-879x2011000700010

Cited by 11 publications

(18 citation statements)

References 9 publications

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“…However, the animal’s age modulated this response, as aged mice showed increased hippocampal expression of Arg1, CD206, SOCS1, and Ym1 in response to IL-4/IL-13 administration relative to adults. These data are in agreement with prior work showing that macrophages from aged mice show increased Arg1 expression in response to IL-4 administration (Cecilio et al, 2011). Similarly, Kumar et al (2013) report that twenty-four hours following a traumatic brain injury (TBI) aged mice showed increased expression of the M2a-associated genes Arg1, Ym1, and CD206 relative to adult mice.…”

Section: Discussionsupporting

confidence: 93%

“…However, less is known about how aging affects the induction of an anti-inflammatory M2 response. The present data confirm that infusion of the anti-inflammatory cytokines IL-4 and IL-13 induces expression of the M2-associated genes, namely, Arg1, Fizz1, CD206, SOCS1, Ym1, TGF-β, and IL-1ra (Butovsky et al, 2005, Cecilio et al, 2011, Pepe et al, 2014). However, the animal’s age modulated this response, as aged mice showed increased hippocampal expression of Arg1, CD206, SOCS1, and Ym1 in response to IL-4/IL-13 administration relative to adults.…”

Section: Discussionsupporting

confidence: 84%

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Differential response to intrahippocampal interleukin-4/interleukin-13 in aged and exercise mice

Littlefield

Kohman

2017

Neuroscience

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Normal aging is associated with low-grade neuroinflammation that results from age-related priming of microglial cells. Further, aging alters the response to several anti-inflammatory factors, including interleukin (IL)-4 and IL-13. One intervention that has been shown to modulate microglia activation in the aged brain, both basally and following an immune challenge, is exercise. However, whether engaging in exercise can improve responsiveness to anti-inflammatory cytokines is presently unknown. The current study evaluated whether prior exercise training increases sensitivity to anti-inflammatory cytokines that promote the M2 (alternative) microglia phenotype in adult (5-month-old) and aged (23-month-old) C57BL/6J mice. After 8 weeks of exercise or control housing, mice received bilateral hippocampal injections of an IL-4/IL-13 cocktail or vehicle. Twenty-four hours later hippocampal samples were collected and analyzed for expression of genes associated with the M1 (inflammatory) and M2 microglia phenotypes. Results show that IL-4/IL-13 administration increased expression of the M2-associated genes Fizz1, Ym1, Arginase-1 (Arg1), SOCS1, IL-1ra, and CD206. In response to IL-4/IL-13 administration, aged mice showed increased hippocampal expression of the M2-related genes Arg1, SOCS1, Ym1, and CD206 relative to adult mice. Aged mice also showed increased expression of IL-1β relative to adults, which was unaffected by wheel running or IL-4/IL-13. Wheel running was found to have modest effects on expression of Ym1 and Fizz1 in aged and adult mice. Collectively, our findings indicate that aged mice show a differential response to anti-inflammatory cytokines relative to adult mice and that exercise has limited effects on modulating this response.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 84%

Differential response to intrahippocampal interleukin-4/interleukin-13 in aged and exercise mice

Littlefield

Kohman

2017

Neuroscience

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“…Many studies have been demonstrated the impact of immunesenescence or age-related immune cell deficiency in MØ functions [9]–[14]. For example, aging impairs production of NO [14] and phagocytic capacity [9], [10], [12] of MØ and reduces their expression of MHC class II [13].…”

Section: Discussionmentioning

confidence: 99%

“…The maturation state influences the functional behavior of MØ; their performance is particularly compromised as they age [9]–[14]. Age-related debilitation is reflected in activities associated with MØ microbicidal function, including impairment in phagocytic ability and in the production of inflammatory cytokines, chemokines and free radicals; additionally, expression of MHCII molecules is diminished, which may contribute to poor CD4 + T cell responses.…”

Section: Introductionmentioning

confidence: 99%

Cellular Renewal and Improvement of Local Cell Effector Activity in Peritoneal Cavity in Response to Infectious Stimuli

et al. 2011

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The peritoneal cavity (PerC) is a singular compartment where many cell populations reside and interact. Despite the widely adopted experimental approach of intraperitoneal (i.p.) inoculation, little is known about the behavior of the different cell populations within the PerC. To evaluate the dynamics of peritoneal macrophage (MØ) subsets, namely small peritoneal MØ (SPM) and large peritoneal MØ (LPM), in response to infectious stimuli, C57BL/6 mice were injected i.p. with zymosan or Trypanosoma cruzi. These conditions resulted in the marked modification of the PerC myelo-monocytic compartment characterized by the disappearance of LPM and the accumulation of SPM and monocytes. In parallel, adherent cells isolated from stimulated PerC displayed reduced staining for β-galactosidase, a biomarker for senescence. Further, the adherent cells showed increased nitric oxide (NO) and higher frequency of IL-12-producing cells in response to subsequent LPS and IFN-γ stimulation. Among myelo-monocytic cells, SPM rather than LPM or monocytes, appear to be the central effectors of the activated PerC; they display higher phagocytic activity and are the main source of IL-12. Thus, our data provide a first demonstration of the consequences of the dynamics between peritoneal MØ subpopulations by showing that substitution of LPM by a robust SPM and monocytes in response to infectious stimuli greatly improves PerC effector activity.

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“…The main reported age-related changes in macrophage functioning include decreased response to pathogens and increased basal expression of pro-inflammatory cytokines [27], which contributes greatly to the general inflammatory phenotype that is observed during aging; decreased killing of intracellular pathogens and decreased capture of antigens [28]; and changes in expression of effector's molecules [29]. Birjandi and colleagues [30] suggests that the splenic structural arrangement undergoes disorganization and negative functional changes occur in several macrophage populations.…”

mentioning

confidence: 99%

Splenic Niche Cells from Young Heterochronic Parabionts Have Decreased Capability to Amplify T-cell Proliferation in Vitro

Shytikov¹

2015

AJBIO

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Abstract:Immune system dysfunction during aging is well documented fact. Changes in the adaptive immune system are the most marked, especially in the T-cell compartment. In multiple preliminary studies it has been shown that parabiosis between 2 animals of different age can induce age-related changes in adaptive immune response and T-cell subpopulation composition of younger animal. In present study we evaluated the age-related changes in functions of rapidly renewing (macrophages) and slowly renewing cells (CD11c + DCs) cells in spleens of young and old parabionts. We observed impaired capacity of splenic adherent cells from younger heterochronic parabionts to co-stimulate proliferation of autologous T-cells in vitro up to the level of old animals. Also we observed negative effect of this splenic cell population on intracellular signaling mechanisms that regulate PHA-activated proliferation of T-cells from young animals: statistically significant decrease of NFκB p65 expression and increased expression of IκBα during early activation events. This fact suggests that splenic macrophages may be involved in the induction of age-related changes of the immune system and they can be prospective target for further investigation.

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

Cited by 11 publications

References 9 publications

Differential response to intrahippocampal interleukin-4/interleukin-13 in aged and exercise mice

Differential response to intrahippocampal interleukin-4/interleukin-13 in aged and exercise mice

Cellular Renewal and Improvement of Local Cell Effector Activity in Peritoneal Cavity in Response to Infectious Stimuli

Splenic Niche Cells from Young Heterochronic Parabionts Have Decreased Capability to Amplify T-cell Proliferation in Vitro

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