Innate immunity in aging: impact on macrophage function

Plowden, Julie; Renshaw-Hoelscher, Mary; Engleman, Carrie; Katz, Jacqueline M.; Sambhara, Suryaprakash

doi:10.1111/j.1474-9728.2004.00102.x

Cited by 375 publications

(263 citation statements)

References 69 publications

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“…There are many circumstances in which the host's immunological environment is altered. These may include various forms of inherent immunodeficiencies; altered immune status due to aging [7][8][9][10][11][12][13][14], as well as results of prior and/or concurrent infections [15][16][17][18][19][20][21][22]. Previously, we have shown that a number of adjuvant formulations differ in their ability to potentiate the immunogenicity of a malaria vaccine under the altered immunological environment created by Interferon-γ and Interleukin-4 knockouts [23].…”

Section: Introductionmentioning

confidence: 99%

Interleukin-6 has differential influence on the ability of adjuvant formulations to potentiate antibody reponses to a Plasmodium falciparum blood-stage vaccine

Hui

Hashimoto

2007

Vaccine

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The efficacy of vaccine adjuvants can be influenced by the immunological environment of the host, depending on the mechanism(s) by which they exert their immunopotentiating activities. Interleukin-6 is a pleiotropic cytokine that has a broad range of biological activities on immune and non-immune cells. We investigated the role of IL-6 on the ability of nine adjuvant formulations to induce antibody responses to the P. falciparum MSP1-19 malaria vaccine, using IL-6 -/-(KO) mice. Results showed that some adjuvants, ie. MPL-SE, CFA/IFA, ISA720/QS21/MPL, depended on IL-6 for their efficacy, while others exhibited increased potency in its absence. The efficacy of adjuvants in the IL-6 KO environment cannot be solely attributed to their ability to stimulate antigen-specific cellular responses, suggesting that other biological activities of IL-6 are also important. The results further suggest that two adjuvants utilized dissimilar pathways to potentiate the same type of immune response.

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Section: Introductionmentioning

confidence: 99%

Interleukin-6 has differential influence on the ability of adjuvant formulations to potentiate antibody reponses to a Plasmodium falciparum blood-stage vaccine

Hui

Hashimoto

2007

Vaccine

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“…Briefly, Walford hypothesized that increased immune genetic diversity and dysfunction of immune system cause aging-related pathophysiological processes with the growth of the age, termedMacrophage, a bridge linking innate and adaptive immune system, shows the dysregulation of chemokine and cytokine secretion, which may result in poor responses to infection and protracted repair processes with aging (Plowden et al 2004). Several experimental evidences have demonstrated that LPS-activated macrophages from aged mice and humans produced more prostaglandin E2 (PGE2) than those from younger individuals Wu et al 1998).…”

mentioning

confidence: 99%

Dysregulated expression of miR-101b and miR-26b lead to age-associated increase in LPS-induced COX-2 expression in murine macrophage

Liú

Wang

et al. 2015

AGE

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Aging is the natural process of decline in physiological structure and function of various molecules, cells, tissues, and organs. Growing evidence indicates that increased immune genetic diversity and dysfunction of immune system cause aging-related pathophysiological process with the growth of age. In the present study, we observed that LPS-induced higher activation of cyclooxygenase (COX)-2 promoter is associated with the upregulated binding activity of nuclear factor kappa B (NF-κB) in peritoneal macrophages of aged mice than young ones. Additionally, COX-2 is a direct target of miR-101b and miR-26b in the macrophages. Significant upregulation of miR-101b and miR26b effectively prevented LPS-induced excessive expression of COX-2 in the young mice. Because these negative regulatory factors were unresponsive to LPS stimulation, the levels of COX-2 were markedly higher in the macrophages of aged mice. Further study showed that NF-κB activation contributed to the increase in the expression of miR-101b and miR-26b in the LPSstimulated macrophages of young mice, but not aged ones. Moreover, histone deacetylase (HDAC) inhibitor trichostatin A (TSA) upregulated expression of miR101b and miR-26b in the aged mouse macrophages only, but not the young cells. This demonstrated that HDAC suppressed the expression of miR-101b and miR-26b in the LPS-treated macrophages of aged mice and contributed to the aging process. TSA-induced increased expression of miR-101b and miR-26b could further suppress COX-2 expression. These findings provide novel evidence on the regulation of immune senescence and miR-101b and miR-26b, which might be promising targets in treating aged-related inflammatory diseases. Epigenetic regulation of the microRNAs (miRNAs) provides an important evidence for the treatment of innate inflammatory disease with HDAC inhibitors in elderly.

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“…The elderly are more susceptible to peripheral infections with increased incidence of disability and mortality rates for individuals 65 years of age and older (Plackett et al, 2004;Plowden et al, 2004). Aging is related to a proinflammatory environment characterized by constitutively elevated levels of several NF-jB-driven proinflammatory cytokines, such as IL-6, IL-1b, and TNFa, in the absence of overt disease conditions, the so-called inflamm-aging (Franceschi et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Dysregulated expression of miR‐146a contributes to age‐related dysfunction of macrophages

Jiang¹,

Xiang²,

Wang

et al. 2011

Aging Cell

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SummaryAge-associated immune dysfunction, characterized by increased systemic levels of cytokines, manifests as an increased susceptibility to infections. Thus, understanding these negative regulators of the immune response has paved the way to delineating signaling pathways that impact immune senescence. In the present study, we found that miR-146a, which negatively regulated the expression of IL-1b and IL-6, was highly expressed in aged mice. However, there was a lack of response to the stimulation of lipopolysaccharide (LPS) and proinflammatory cytokines in macrophages of aged mice. As a result, the negative feedback regulation loop with miR-146a involving down-regulation of inflammation factors was interrupted in aged mice. Aberrant NF-jB binding to the miR-146a promoter was demonstrated to be associated with the abnormal expression of miR-146a in aged mice. The DNA methyltransferase inhibitor (5-aza-2-deoxycytidine) and the histone deacetylase inhibitor [trichostatin A (TSA)] both significantly up-regulated miR-146a transcriptional activation by altering the DNA-binding activity of NF-jB in macrophages isolated from aged mice, which suggests that DNA methylation and histone acetylation are involved in the suppression of age-dependent miR-146a expression. Additionally, high levels of histone deacetylase (HDACs) expressions contributed to the inhibition of miR-146a expression in LPS-stimulated macrophages from aged mice in vitro. While the suppression of HDACs activities by TSA could improve LPS-induced inflammatory responses owing to up-regulation of miR-146a expression in macrophages from aged mice. These data indicate that the dysregulated expression of miR-146a results in the age-associated dysfunction of macrophages, and miR-146a may be a good target for the treatment of age-related inflammatory diseases.

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Innate immunity in aging: impact on macrophage function

Cited by 375 publications

References 69 publications

Interleukin-6 has differential influence on the ability of adjuvant formulations to potentiate antibody reponses to a Plasmodium falciparum blood-stage vaccine

Interleukin-6 has differential influence on the ability of adjuvant formulations to potentiate antibody reponses to a Plasmodium falciparum blood-stage vaccine

Dysregulated expression of miR-101b and miR-26b lead to age-associated increase in LPS-induced COX-2 expression in murine macrophage

Dysregulated expression of miR‐146a contributes to age‐related dysfunction of macrophages

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