Resident macrophages initiating and driving inflammation in a monosodium urate monohydrate crystal–induced murine peritoneal model of acute gout

Martin, William J.; Walton, Michaela C.; Harper, Jacquie L.

doi:10.1002/art.24185

Cited by 206 publications

(191 citation statements)

References 21 publications

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“…In an animal model of gout, wild-type mice pretreated with the IL-1 inhibitor rilonacept demonstrated attenuated inflammation after MSU injection into the ankle joint. 110 111 Correspondingly, mice deficient in IL-1 receptor failed to develop gout-like symptoms fully after MSU injection. 110 111 The recent finding of NALP3 inflammasome in sensing MSU deposition and subsequent activation of the downstream innate immune response further demonstrates a role of IL-1b in gout pathogenesis and hyperalgesia.…”

Section: Goutmentioning

confidence: 99%

“…For instance, macrophages initiate the inflammatory response to MSU crystals and produce inflammatory cytokines and chemokines that induce migration of blood monocytes to amplify the inflammatory response further. 110 Neutrophil influx into the synovium and joint fluid is the pathological hallmark of acute gout. 112 113 It is clear that NALP3 is expressed in all these cell types, with the capability to activate an inflammasome-mediated response.…”

Section: Goutmentioning

confidence: 99%

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The inflammasome as a target for pain therapy

Zhang¹,

Li²,

Li³

et al. 2016

British Journal of Anaesthesia

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The interleukin-1 family of cytokines are potent inducers of inflammation and pain. Proteolytic activation of this family of cytokines is under the control of several innate immune receptors that coordinate to form large multiprotein signalling platforms, termed inflammasomes. Recent evidence suggests that a wide range of inflammatory diseases, cancers, and metabolic and autoimmune disorders, in which pain is a common complaint, may be coordinated by inflammasomes. Activation of inflammasomes results in cleavage of caspase-1, which subsequently induces downstream initiation of several potent pro-inflammatory cascades. Therefore, it has been proposed that targeting inflammasome activity may be a novel and effective therapeutic strategy for these pain-related diseases. The purpose of this narrative review article is to provide the reader with an overview of the activation and regulation of inflammasomes and to investigate the potential therapeutic role of inflammasome inhibition in the treatment of diseases characterized by pain, including the following: complex regional pain syndrome, gout, rheumatoid arthritis, inflammatory pain, neuropathic pain, chronic prostatitis, chronic pelvic pain syndrome, and fibromyalgia. We conclude that the role of the inflammasome in pain-associated diseases is likely to be inflammasome subtype and disease specific. The currently available evidence suggests that disease-specific targeting of the assembly and activity of the inflammasome complex may be a novel therapeutic opportunity for the treatment of refractory pain in many settings.

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Section: Goutmentioning

confidence: 99%

Section: Goutmentioning

confidence: 99%

The inflammasome as a target for pain therapy

Zhang¹,

Li²,

Li³

et al. 2016

British Journal of Anaesthesia

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“…This finding provides further evidence that the resident macrophage, rather than the newly recruited monocytes, initiates the primary phase of inflammation in vivo (5). The lack of proinflammatory activity by early-recruited monocytes appears to be primarily associated with low levels of proIL-1␤.…”

Section: Discussionmentioning

confidence: 51%

“…MSU crystals were prepared and characterized as previously described (5). All MSU crystals were determined to be endotoxin free by Limulus amebocyte cell lysate assay (Ͻ0.01 endotoxin units/10 mg).…”

Section: Methodsmentioning

confidence: 99%

“…However, other studies show that MSU crystals induce a classic proinflammatory response in both primary and bone marrow-derived macrophages (3,4,(11)(12)(13)(14), indicating a key role for macrophages in the initiation of the inflammatory cascade. In addition, there is evidence to suggest that upon recruitment to the site of inflammation, early infiltrating monocytes do not exhibit a proinflammatory phenotype and therefore may not be driving the early phase of inflammation in gout (5). Together, these findings raise questions about the true functional phenotypes expressed by MSU crystalrecruited monocyte/macrophage populations in vivo.…”

mentioning

confidence: 99%

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Monosodium urate monohydrate crystal–recruited noninflammatory monocytes differentiate into M1‐like proinflammatory macrophages in a peritoneal murine model of gout

Martin

Shaw

Liu

et al. 2011

Arthritis & Rheumatism

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Objective. To profile monosodium urate monohydrate (MSU) crystal-recruited monocyte inflammatory function during the course of in vivo differentiation, in a murine model of peritoneal MSU crystal-induced inflammation.Methods. C57BL/6J mice were injected intraperitoneally with MSU crystals, and the peritoneal cells were harvested at different time points. The MSU crystal-recruited monocyte/macrophage population was analyzed for the expression of differentiation and activation markers, cytokine production following MSU crystal restimulation ex vivo and in vivo, expression of NLRP3-associated proteins (ASC, caspase 1) and prointerleukin-1␤ (proIL-1␤), and phagocytic capacity.Results. Monocytes recruited 8 hours after MSU crystal stimulation (F4/80 low Gr-1 int 7/4؉) exhibited poor phagocytic capacity, expressed low levels of proIL-1␤, and failed to produce proinflammatory cytokines in response to MSU crystal restimulation. In the absence of MSU crystal restimulation, differentiating monocytes produced low levels of transforming growth factor ␤1 ex vivo, and this was abrogated following MSU crystal restimulation. Over time these cells developed a proinflammatory phenotype in vivo, characterized by the production of IL-1␤, tumor necrosis factor ␣, IL-6, CCL2 (monocyte chemotactic protein 1), and CXCL1 (cytokine-induced neutrophil chemoattractant) following ex vivo MSU crystal restimulation, and leading to IL-1␤ production and cell infiltration following MSU crystal rechallenge in vivo. Proinflammatory function was associated with differentiation toward a macrophage phenotype (F4/80 high Gr-1-7/4-), an increase in phagocytic capacity, and an increase in the expression of proIL-1␤. Conclusion. MSU crystal-recruited monocytes differentiate into proinflammatory M1-like macrophages in vivo. This proinflammatory macrophage phenotype is likely to play a key role in perpetuating inflammation in gouty arthritis in the presence of ongoing deposition of fresh MSU crystals.Acute gout is an intensely painful form of inflammatory arthritis caused by the formation of monosodium urate monohydrate (MSU) crystals in the joint and connective tissues. An acute attack of gout is characterized by intense pain and swelling and reddening of the skin around the affected area. Without treatment this inflammatory response will resolve naturally over 7-10 days.Interleukin-1␤ (IL-1␤) has been identified as a pivotal cytokine in gout and MSU crystal-induced inflammation (1-3). More recently, studies have identified IL-1␤ production following activation of the NLRP3 inflammasome in resident macrophages as a key event in the initiation of an attack of acute gout (4-7). However, there is a growing body of evidence indicating that cells of the monocyte/macrophage lineage play a pivotal role not only in the initiation but also in the progression and resolution of acute gouty inflammation.It has been proposed that the self-limiting nature of an acute gout attack is linked to the differentiation state of the MSU crystal-recruited monocyte population. In...

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Inflammation and Wound Healing

Turabelidze¹,

DiPietro²

2012

Oral Wound Healing

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Resident macrophages initiating and driving inflammation in a monosodium urate monohydrate crystal–induced murine peritoneal model of acute gout

Cited by 206 publications

References 21 publications

The inflammasome as a target for pain therapy

The inflammasome as a target for pain therapy

Monosodium urate monohydrate crystal–recruited noninflammatory monocytes differentiate into M1‐like proinflammatory macrophages in a peritoneal murine model of gout

Inflammation and Wound Healing

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