Macrophage Derived Platelet Activating Factor Implicated in the Resolution Phase of Gouty Inflammation

Yagnik, Darshna

doi:10.1155/2014/526496

Cited by 9 publications

(9 citation statements)

References 34 publications

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“…In this study we have demonstrated that recombinant PAF-AH treatment may tip the inflammatory balance in favour of inflammation resolution as it was able to decrease monocyte derived IL-1β and IL-6 secretion due to MSU crystal stimulation. These results are consistent with our previous study in which PAF was upregulated by monocytes in response to MSU crystals (9) and recombinant PAF-AH administration downregulated TNFα secretion. The exact form of PAF was not characterised; we propose that this was probably inert lysosomal PAF.…”

Section: Discussionsupporting

confidence: 93%

“…We investigated whether the activity of recombinant PAF-AH could also modify IL-1β and IL-6 secretion. Previously, we had reported that recombinant PAF-AH decreases TNFα cytokine secretion from immature human monocytes in a similar experimental model (9).…”

Section: Tre a T M E N T Wi T H Rec O M B I N A N T Pa F-a H I N H I mentioning

confidence: 80%

“…This response is driven in part by NLRP3 inflammasome activation via NOD-like receptors which activate interleukin-1β (IL-1β) release (5)(6)(7). Studies in vitro suggest that MSU crystals may induce tumour necrosis factor α (TNFα), IL-1β, IL-6, platelet-activating factor (PAF) secretion in undifferentiated monocytes which in turn may promote endothelial E-selectin expression and secondary neutrophil adhesion (8)(9)(10). Conversely, differentiated macrophages are able to uptake MSU crystals and release transforming growth factor β1 (TGFβ1), a powerful inhibitor of inflammation (11).…”

Section: Introductionmentioning

confidence: 99%

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Urate crystals induce macrophage PAF‑AH secretion which is differentially regulated by TGFβ1 and hydrocortisone

Yagnik

Hills

2018

Mol Med Report

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The aim of the present study was to establish the role of platelet‑activating factor acetyl hydrolase (PAF‑AH) in the resolution phase of gout using an established in vitro mononuclear cell model. The effects of signalling pathway inhibitors on PAF‑AH secretion, as well as the effects of the common treatments hydrocortisone and colchicine, an antibody against the anti‑inflammatory cytokine transforming growth factor β1 (TGFβ1), and the transcriptional inhibitor actinomycin D, were also investigated. The effect of recombinant PAF‑AH on cytokine secretion by these cells was also determined. Human peripheral blood‑derived monocytes were isolated and differentiated into macrophages. Monocytes and macrophages were stimulated with monosodium monohydrate urate (MSU) crystals or lipopolysaccharide in the presence or absence of AEG3482 [a c‑Jun N‑terminal kinase (JNK) inhibitor], MG132 (a proteasome inhibitor), hydrocortisone or colchicine. Cultures were then analysed for PAF‑AH secretion using ELISA. A 6‑fold upregulation of PAF‑AH secretion was observed following macrophage exposure to MSU crystals for 24 h (29.3±6 vs. 5.4±0.3 ng/ml unstimulated; P<0.05). Following 72 h, PAF‑AH levels decreased significantly (11.1±1.8; P<0.01). Secretion was further enhanced following pre‑treatment with the JNK protein kinase inhibitor AEG3482 prior to MSU crystal stimulation (P<0.05) and was abrogated when cells were preincubated with actinomycin D or the proteasome inhibitor MG132 (50, 100 and 200 µM). The addition of recombinant PAF‑AH (2.5‑10 ng/ml) to MSU crystal‑stimulated immature monocyte cultures significantly decreased pro‑inflammatory interleukin (IL)‑1β (unstimulated 687±124 vs. stimulated 113±30 pg/ml) and IL‑6 secretion (unstimulated 590±50 vs. stimulated 182±19 pg/ml). Treatment of MSU crystal‑stimulated macrophages with hydrocortisone (2 µM) also significantly decreased PAF‑AH release (P<0.05). Neutralising anti‑TGFβ1 addition decreased PAF‑AH dose‑dependently with the highest inhibition observed at 1 µg/ml (P<0.05). The results implicated that PAF‑AH may have an anti‑inflammatory role in the resolution phase of gout.

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Section: Discussionsupporting

confidence: 93%

Section: Tre a T M E N T Wi T H Rec O M B I N A N T Pa F-a H I N H I mentioning

confidence: 80%

Section: Introductionmentioning

confidence: 99%

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Urate crystals induce macrophage PAF‑AH secretion which is differentially regulated by TGFβ1 and hydrocortisone

Yagnik

Hills

2018

Mol Med Report

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“…However, previous studies in other organs provided hints that platelets may not only be important for the propagation of vascular inflammation. It could be shown that platelet activating factor (PAF) plays a role in mediating the uptake of urate crystals during the resolution of gouty inflammation ( 152 ). Platelets are also a major source for anti-inflammatory mediators of the lipoxin family, e.g., specialized pro-resolving mediators (SPMs) such as resolvins and maresins ( 153 ).…”

Section: Introductionmentioning

confidence: 99%

Role of Platelets in Leukocyte Recruitment and Resolution of Inflammation

2018

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Platelets are most often recognized for their crucial role in the control of acute hemorrhage. However, current research has greatly expanded the appreciation of platelets beyond their contribution to primary hemostasis, indicating that platelets also actively participate in leukocyte recruitment and the regulation of the host defense in response to exogenous pathogens and sterile injury. Early recruitment of leukocytes, especially neutrophils, is the evolutionary stronghold of the innate immune response to successfully control exogenous infections. Platelets have been shown to physically interact with different leukocyte subsets during inflammatory processes. This interaction holds far-reaching implications for the leukocyte recruitment into peripheral tissues as well as the regulation of leukocyte cell autonomous functions, including the formation and liberation of neutrophil extracellular traps. These functions critically depend on the interaction of platelets with leukocytes. The host immune response and leukocyte recruitment must be tightly regulated to avoid excessive tissue and organ damage and to avoid chronification of inflammation. Thus, platelet-leukocyte interactions and the resulting leukocyte activation and recruitment also underlies tight regulation by several inherited feedback mechanisms to limit the extend of vascular inflammation and to protect the host from collateral damage caused by overshooting immune system activation. After the acute inflammatory phase has been overcome the host defense response must eventually be terminated to allow for resolution from inflammation and restoration of tissue and organ function. Besides their essential role for leukocyte recruitment and the initiation and propagation of vascular inflammation, platelets have lately also been implicated in the resolution process. Here, their contribution to phagocyte clearance, T cell recruitment and macrophage reprogramming is also of outmost importance. This review will focus on the role of platelets in leukocyte recruitment during the initiation of the host defense and we will also discuss the participation of platelets in the resolution process after acute inflammation.

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“…In vitro experiments demonstrated that MSU crystal-stimulated macrophages release PAF, which in turn downregulates the TNF secretion (Yagnik, 2014). …”

Section: Introductionmentioning

confidence: 99%

How Factors Involved in the Resolution of Crystal-Induced Inflammation Target IL-1β

Oliviero

Scanu

2017

Front. Pharmacol.

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One of the main clinical features characterizing crystal-induced inflammation is its spontaneous resolution. The aim of this review is to outline the various factors involved in the self-limiting course of crystal-induced inflammation focusing on their effect on IL-1β production. Endogenous molecules that are induced or locally recruited by the process itself, inhibitory proteins naturally present in the joint and exogenous dietary factors are discussed. Aside from the classical well-known molecules involved in the resolution of crystal-induced acute attack such as TGFβ, IL-10, IL-1Ra, and lipoproteins, particular attention is paid to recently uncovered mechanisms such as the aggregation of neutrophil extracellular traps, the release of ectosomes from neutrophil surface, and alpha-1-anti-trypsin-mediated IL-1 inhibition.

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Macrophage Derived Platelet Activating Factor Implicated in the Resolution Phase of Gouty Inflammation

Cited by 9 publications

References 34 publications

Urate crystals induce macrophage PAF‑AH secretion which is differentially regulated by TGFβ1 and hydrocortisone

Urate crystals induce macrophage PAF‑AH secretion which is differentially regulated by TGFβ1 and hydrocortisone

Role of Platelets in Leukocyte Recruitment and Resolution of Inflammation

How Factors Involved in the Resolution of Crystal-Induced Inflammation Target IL-1β

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