Advanced Glycation End Products Modulate the Maturation and Function of Peripheral Blood Dendritic Cells

Price, Claire; Sharp, Patrick; North, M. E.; Rainbow, S; Knight, Stella C.

doi:10.2337/diabetes.53.6.1452

Cited by 45 publications

(35 citation statements)

References 34 publications

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“…Because IL-12 and IFN-␥ released by activated DCs contributed to the formation of atherosclerotic lesions and plaque destabilization, 18,19 our findings suggest that AGEs might promote the atherosclerosis by enhancing the maturation and immunity of DCs. Quite recently, Price et al 20 reported that AGEs prohibited the maturation of DCs and AGE-treated DCs had a loss in T-cell stimulation capacity, which is different from our present study. Although we do not know the reason for the discrepancy at present, there might be several possibilities.…”

Section: Discussioncontrasting

confidence: 99%

Advanced Glycosylation End Products Might Promote Atherosclerosis Through Inducing the Immune Maturation of Dendritic Cells

Jia

Liang

et al. 2005

ATVB

118

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Objective-Both advanced glycosylation end products (AGEs) and dendritic cells (DCs) have been shown to play a causative role in atherosclerosis. However, whether they function interactively in the process remains uncertain. We therefore studied the effects of AGE-bovine serum albumin (AGE-BSA) on the maturation of DCs and the expressions of scavenger receptor-A (SR-A) and receptor for AGEs (RAGE) on DCs. Key Words: advanced glycosylation end products Ⅲ atherosclerosis Ⅲ dendritic cells Ⅲ immunity Ⅲ receptor for advanced glycosylation end products D iabetes is associated with severe atherosclerosis and cardiovascular diseases that account for a high mobility and mortality in industrialized countries. 1 It is therefore very important for us to understand the mechanisms of how the diseases occur. Advanced glycosylation end products (AGEs) (long-term products of the Maillard reaction) have been shown to play a causative role in diabetic vasculopathy and atherosclerosis. 2,3 In diabetic atherosclerotic lesions, not only the deposition of AGEs but also the colocalization of AGEs antigen and AGEs receptors (scavenger receptor A [SR-A], receptor for AGEs [RAGE]) were found. 2,3 Additionally, accumulating evidences have suggested that dendritic cells (DCs) also play a crucial role in atherosclerosis 4 by activating T-cell in atherosclerosis. 5 Proinflammatory factors can promote maturation of DCs corresponding to a switch from a phagocytic stage to a stage of strong T cell-stimulatory capacity. The interactive roles of AGEs and DCs remain unknown now. We therefore examined the effect of advanced glycosylation end-bovine serum albumin (AGE-BSA) on DCs maturation, cytokine secretion, and SR-A and RAGE expression. MethodsThe informed consent was obtained from all volunteers and the study protocol was approved by our institutional ethical committee.

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Section: Discussioncontrasting

confidence: 99%

Advanced Glycosylation End Products Might Promote Atherosclerosis Through Inducing the Immune Maturation of Dendritic Cells

Jia

Liang

et al. 2005

ATVB

118

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“…Diabetes and aging in particular are associated with a deregulated and less effective immune response. Interestingly, advanced glycation end products down-regulate in vitro the ability of DCs to express costimulatory signals and to activate T cells (39). Similar results have been described after blockade of the autocrine secretion of HMGB1 and of RAGE activation (9,23,37).…”

Section: Discussionsupporting

confidence: 61%

Maturing Dendritic Cells Depend on RAGE for In Vivo Homing to Lymph Nodes

Manfredi¹,

Capobianco²,

Esposito³

et al. 2008

The Journal of Immunology

101

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The mobilization of dendritic cells (DCs) from peripheral tissues is critical for the establishment of T cell-dependent immune responses or tolerance, because the physical interaction of DCs with naive T cells takes place in the T cell areas of lymph nodes. The autocrine/paracrine release of the high mobility group box 1 (HMGB1) nuclear protein by DCs controls the outcome of the DC–T cell interaction, influencing the priming/Th1 polarization of naive T cells. We herein present evidence that the receptor for advanced glycation end products (RAGE), a multiligand member of the Ig superfamily of cell-surface molecules that acts as a receptor for HMGB1, plays a nonredundant role in DC homing to lymph nodes. We used noninvasive imaging by magnetic resonance and immunohistochemistry to track DCs after s.c. injection in the footpad of wild-type+/+ or RAGE−/− mice. Maturing DCs expressing RAGE effectively migrated in both conditions. In contrast, RAGE−/− DCs failed to reach the draining popliteal lymph nodes of +/+ and −/− mice, indicating that the integrity of RAGE is required for DC mobilization. Thus the HMGB1-RAGE pathway is a checkpoint in DC maturation and function and a candidate for targeted therapies.

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“…The effect of AGE molecules on DC phenotype still remains controversial. Indeed, Price et al (58) observed a dosedependent inhibition of CD83 expression on DCs exposed to AGE peptide, associated with the loss of their capacity to stimulate primary proliferation of allogeneic T cells. In contrast, Ge et al (31) have shown that AGE induced a dose-and time-dependent maturation of DCs as indicated by the expression of CD83.…”

Section: Discussionmentioning

confidence: 99%

Advanced Glycation End Products Inhibit Both Infection and TransmissionIn Transof HIV-1 from Monocyte-Derived Dendritic Cells to Autologous T Cells

Nasreddine

Borde

Gozlan

et al. 2011

The Journal of Immunology

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Highly active antiretroviral therapy is associated with carbohydrate metabolic alterations that may lead to diabetes. One consequence of hyperglycemia is the formation of advanced glycation end products (AGEs) that are involved in diabetes complications. We investigated the impact of AGEs on the infection of monocyte-derived dendritic cells (MDDCs) by HIV-1 and the ability of MDDCs to transmit the virus to T cells. We showed that AGEs could inhibit infection of MDDCs with primary R5-tropic HIV-1Ba-L by up to 85 ± 9.2% and with primary X4-tropic HIV-1VN44 by up to 60 ± 8.5%. This inhibitory effect of AGEs was not prevented by a neutralizing anti-receptor for advanced glycation end products (anti-RAGE) Ab, demonstrating a RAGE-independent mechanism. Moreover, AGEs inhibited by 70–80% the transmission in trans of the virus to CD4 T cells. Despite the inhibitory effect of AGEs on both MDDC infection and virus transmission in trans, no inhibition of virus attachment to cell membrane was observed, confirming that attachment and transmission of the virus involve independent mechanisms. The inhibitory effect of AGEs on infection was associated with a RAGE-independent downregulation of CD4 at the cell membrane and by a RAGE-dependent repression of the CXCR4 and CCR5 HIV-1 receptors. AGEs induce the secretion of proinflammatory cytokines IL-6, TNF-α, and IL-12, but not RANTES or MIP-1α, and did not lead to MDDC maturation as demonstrated by the lack of expression of the CD83 molecule. Taken together, our results suggest that AGEs can play an inhibiting role in HIV-1 infection in patients who accumulate circulating AGEs, including patients treated with protease inhibitors that developed diabetes.

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Advanced Glycation End Products Modulate the Maturation and Function of Peripheral Blood Dendritic Cells

Cited by 45 publications

References 34 publications

Advanced Glycosylation End Products Might Promote Atherosclerosis Through Inducing the Immune Maturation of Dendritic Cells

Advanced Glycosylation End Products Might Promote Atherosclerosis Through Inducing the Immune Maturation of Dendritic Cells

Maturing Dendritic Cells Depend on RAGE for In Vivo Homing to Lymph Nodes

Advanced Glycation End Products Inhibit Both Infection and TransmissionIn Transof HIV-1 from Monocyte-Derived Dendritic Cells to Autologous T Cells

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