Tissue resident macrophages: Key players in the pathogenesis of type 2 diabetes and its complications

Meshkani, Reza; Vakili, Sanaz

doi:10.1016/j.cca.2016.08.015

Cited by 118 publications

(96 citation statements)

References 151 publications

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“…Other regularly cited markers of M2 macrophages are resistin-like β (Fizz1), CD301, Retnla, Dectin-1, MGL-1, peroxisome proliferator activated receptor (PPAR)γ and pSTAT6[16]. Also, several cytokines, mostly with immunosuppressive characteristics, produced by M2 cells, include IL-10, transforming growth factor β (TGF-β) and some chemokines (CCL17, 18, 22 and 24)[16,20,21]. …”

Section: Role Of Infiltrating Macrophages In Lean and Obese Atmentioning

confidence: 99%

Role of pro- and anti-inflammatory phenomena in the physiopathology of type 2 diabetes and obesity

Pirola¹,

Ferraz²

2017

WJBC

103

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In obesity, persistent low-grade inflammation is considered as a major contributor towards the progression to insulin resistance and type 2 diabetes while in lean subjects the immune environment is non-inflammatory. Massive adipose tissue (AT) infiltration by pro-inflammatory M1 macrophages and several T cell subsets as obesity develops leads to the accumulation - both in the AT and systemically - of numerous pro-inflammatory cytokines, including interleukin-1β (IL-1β), tumor necrosis factor α, IL-17 and IL-6 which are strongly associated with the progression of the obese phenotype towards the metabolic syndrome. At the same time, anti-inflammatory M2 macrophages and Th subsets producing the anti-inflammatory cytokines IL-10, IL-5 and interferon-γ, including Th2 and T-reg cells are correlated to the maintenance of AT homeostasis in lean individuals. Here, we discuss the basic principles in the control of the interaction between the AT and infiltrating immune cells both in the lean and the obese condition with a special emphasis on the contribution of pro- and anti-inflammatory cytokines to the establishment of the insulin-resistant state. In this context, we will discuss the current knowledge about alterations in the levels on pro- and anti-inflammatory cytokines in obesity, insulin resistance and type 2 diabetes mellitus, in humans and animal models. Finally, we also briefly survey the recent novel therapeutic strategies that attempt to alleviate or reverse insulin resistance and type 2 diabetes via the administration of recombinant inhibitory antibodies directed towards some pro-inflammatory cytokines.

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Section: Role Of Infiltrating Macrophages In Lean and Obese Atmentioning

confidence: 99%

Role of pro- and anti-inflammatory phenomena in the physiopathology of type 2 diabetes and obesity

Pirola¹,

Ferraz²

2017

WJBC

103

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“…The pro‐inflammatory and antimicrobial M1 macrophages secreted pro‐inflammatory mediators such as nitric oxide (NO), interleukin‐1 (IL‐1) and tumour necrosis factor (TNF), conferring an aberrant inflammation . Of note was that a substantial activation of tissue macrophages was observed in T2D and its complications, including diabetic nephropathy (DN) and retinopathy (DR) . Moreover, the evidence that the cell numbers, morphology, and innate immunity functions of resident peritoneal macrophages were significantly altered in mice with long‐term T2D .…”

Section: Introductionmentioning

confidence: 99%

Suppression of TLR4 by miR-448 is involved in Diabetic development via regulating Macrophage polarization

Zhao

Wang

et al. 2019

Journal of Pharmacy and Pharmacology

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Objectives Lipopolysaccharide (LPS) contributed to the development and progression of type 2 diabetes mellitus (T2D), while TLR4 is reported to mediate the LPS‐induced inflammation in macrophages. However, the potential molecular mechanisms for TLR4‐mediated macrophages activation in T2D have not yet to be fully clarified. Methods Type 2 diabetes models in C57BL/6J mice were generated by a combination administration of streptozotocin (STZ) and a high‐fat diet (HFD). Cell proportions of M1 and M2 macrophages were analyzed using flow cytometry. Expression profiles of miR‐448 and TLR 4 were determined by qRT‐PCR and Western blot. Key findings LPS/IFN‐γ significantly induced M1 polarization in macrophages characterized by the increased levels of TNF‐α, IL‐6, IL‐12, iNOS and decreased levels of TNF‐β, CCL‐22, IL‐10 and Arg‐1, with a higher expression of toll‐like receptor 4 (TLR4) in vitro. Consistently, T2D mice‐derived macrophages had a significantly elevated expression of TLR4 mRNA and decreased expression of miR‐448. We further confirmed that miR‐448 could inhibit TLR4 expression by targeting the 3′‐UTR of TLR4, rescuing the LPS/IFN‐γ‐induced M1 macrophage polarization. Conclusions Taken together, our results indicated that decreased miR‐448 in diabetic macrophages may contribute to LPS‐induced M1 polarization by targeting TLR4, thereby modulating T2D development.

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“…Macrophages are immune cells that are ubiquitously expressed across tissues and play an important role in the development and resolution of the inflammatory response. For instance, exposure to bacterial lipopolysaccharide (LPS) induces an inflammatory phenotype in macrophages that is characterised by the expression of many proinflammatory cytokines including TNF-α and IL-1β [4]. The proinflammatory activities of macrophages is also associated with activation of NLR Family Pyrin Domain Containing 3 (NLRP3)-dependent inflammasome [5] and the nuclear transcription factor, NF-κB [6].…”

Section: Introductionmentioning

confidence: 99%

TET-2 up-regulation is associated with the anti-inflammatory action of Vicenin-2

et al. 2018

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Vicenin-2, a C-glycoside flavone that is present in many plant sources, exerts potent antiinflammatory effects in a number of cell and animal models of inflammation. Ten-eleven translocation (TET)-2 has recently gained considerable attention due to the role it plays in regulating the inflammasome. We studied the ability of Vicenin-2 (V-2) to regulate a range This study demonstrates that the anti-inflammatory actions of V-2 are associated not only with increased IL-10 and IL-1Ra expression but also with TET-2 expression. Further work is required to establish if the effects of V-2 can be definitively linked to TET-2 activity and that these actions are mirrored in a range of relevant cell types.

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Tissue resident macrophages: Key players in the pathogenesis of type 2 diabetes and its complications

Cited by 118 publications

References 151 publications

Role of pro- and anti-inflammatory phenomena in the physiopathology of type 2 diabetes and obesity

Role of pro- and anti-inflammatory phenomena in the physiopathology of type 2 diabetes and obesity

Suppression of TLR4 by miR-448 is involved in Diabetic development via regulating Macrophage polarization

TET-2 up-regulation is associated with the anti-inflammatory action of Vicenin-2

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