Macrophage Migration Inhibitory Factor Regulates U1 Small Nuclear RNP Immune Complex–Mediated Activation of the NLRP3 Inflammasome

Shin, Min Sun; Kang, Youna; Wahl, Elizabeth; Park, Hong‐Jai; Lazova, Rossitza; Leng, Lin; Mamula, Mark J.; Krishnaswamy, Smita; Bucala, Richard; Kang, Insoo

doi:10.1002/art.40672

Cited by 62 publications

(63 citation statements)

References 56 publications

(94 reference statements)

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“…Similar to our observations, exogenous MIF did not activate NLRP3 in murine BMDM; however, endogenous MIF regulated NLRP3 in the assembly of inflammasomes [17]. Furthermore, a study using a murine systemic lupus erythematosus model confirmed that addition of exogenous rMIF alone did not induce NLRP3 in human monocytes [37]. Although exogenously added rMIF had no impact on monocyte IL-1b production in our model, MIF may act on other inflammatory pathways which were not investigated in this study.…”

Section: Discussionsupporting

confidence: 86%

Soluble mediators in packed red blood cells augment lipopolysaccharide‐induced monocyte interleukin‐1β production

et al. 2020

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Background and objectives Soluble mediators in packed red-blood-cell (PRBC) units have been hypothesized as a mechanism associated with transfusion-related immune modulation. Soluble mediators including damage-associated molecular patterns (DAMPs) are known to activate inflammasomes. Inflammasome complexes maturate caspase-1 and interleukin (IL)-1b. We assessed whether PRBC supernatants (SN) modulated IL-1b driven inflammation and whether macrophage migration inhibitory factor (MIF) was a contributing factor. Materials and methods Isolated monocytes were incubated with PRBC-SN in an in vitro transfusion model. Lipopolysaccharide (LPS) was added in parallel to model a bacterial infection. Separately, recombinant MIF was used in the model to assess its role in IL-1b driven inflammation. IL-1b and caspase-1 were quantified in the PRBC-SN and culture SN from the in vitro model. Results PRBC-SN alone did not induce IL-1b production from monocytes. However, PRBC-SN alone increased caspase-1 production. LPS alone induced both IL-1b and caspase-1 production. PRBC-SN augmented LPS-driven IL-1b and caspase-1 production. Recombinant MIF did not modulate IL-1b production in our model. Conclusions Soluble mediators in PRBC modulate monocyte IL-1b inflammation, which may be a contributing factor to adverse effects of transfusion associated with poor patient outcomes. While MIF was present in PRBC-SN, we found no evidence that MIF was responsible for IL-1b associated immune modulation.

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Section: Discussionsupporting

confidence: 86%

Soluble mediators in packed red blood cells augment lipopolysaccharide‐induced monocyte interleukin‐1β production

et al. 2020

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“…In turn, a variety of signaling cascades, including the MAPK, PI3K/AKT, and NF-kB pathways are activated. By doing so, MIF activates pro-inflammatory events including the secretion of IL-6 and TNF-α and the activation of the inflammasome [29][30][31].…”

Section: Biology Physiology and Physiopathology Of Mifmentioning

confidence: 99%

The Role of Macrophage Migration Inhibitory Factor in Alzheimer′s Disease: Conventionally Pathogenetic or Unconventionally Protective?

et al. 2020

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Recent preclinical and clinical observations have offered relevant insights on the etiopathogenesis of late onset Alzheimer′s disease (AD) and upregulated immunoinflammatory events have been described as underlying mechanisms involved in the development of AD. Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine produced by several cells of the innate and adaptive immune system, as well as non-immune cells. In the present review, we highlight experimental, genetic, and clinical studies on MIF in rodent models of AD and AD patients, and we discuss emerging therapeutic opportunities for tailored modulation of the activity of MIF, that may potentially be applied to AD patients. Dismantling the exact role of MIF and its receptors in AD may offer novel diagnostic and therapeutic opportunities in AD.

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“…Recently, the role of macrophage migration inhibitory factor (MIF) in up‐regulating NLRP3 expression was demonstrated in human monocytes stimulated with the U1 snRNP lupus immune complex . Upon exposure to the latter, human monocytes produced MIF, and blocking MIF binding to its receptor CD74 suppressed NLRP3 expression and subsequent caspase 1 activation . The expression levels of MIF and CD74 correlated at the single cell level, supporting the autocrine and paracrine effects of MIF in regulating NLRP3.…”

Section: Introductionmentioning

confidence: 94%

“…Also, ATP‐induced IL‐1β production has been shown to be increased in the macrophages of patients with SLE . Recently, the role of macrophage migration inhibitory factor (MIF) in up‐regulating NLRP3 expression was demonstrated in human monocytes stimulated with the U1 snRNP lupus immune complex . Upon exposure to the latter, human monocytes produced MIF, and blocking MIF binding to its receptor CD74 suppressed NLRP3 expression and subsequent caspase 1 activation .…”

Section: Introductionmentioning

confidence: 99%

Advances in Disease Mechanisms and Translational Technologies: Clinicopathologic Significance of Inflammasome Activation in Autoimmune Diseases

Kahlenberg

Kang

2020

Arthritis & Rheumatology

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Autoimmune diseases are characterized by dysregulated immune tolerance to self and inflammatory damage to tissues and organs. The development of inflammation involves multiple innate and adaptive immune pathways. Inflammasomes are multimeric cytosolic protein complexes that form to mediate host immune responses upon recognizing pathogen‐ or damage‐associated molecular patterns via pattern‐recognition receptors (PRRs). The accelerating pace of inflammasome research has demonstrated important roles for inflammasome activation in many pathologic conditions, including infectious, metabolic, autoinflammatory, and autoimmune diseases. The inflammasome generally comprises a PRR, procaspase 1, and an adaptor molecule connecting the PRR and procaspase 1. Upon inflammasome activation, procaspase 1 becomes active caspase 1 that converts pro–interleukin‐1β (proIL‐1β) and proIL‐18 into mature and active IL‐1β and IL‐18, respectively. The cytokines IL‐1β and IL‐18 have multipotent effects on immune and nonimmune cells and induce and promote systemic and local inflammatory responses. Human studies have shown increased levels of these cytokines, altered activation of inflammasome‐related molecules, and/or the presence of inflammasome activators in rheumatic diseases, including systemic lupus erythematosus, rheumatoid arthritis, crystal‐induced arthropathies, and Sjögren's syndrome. Such changes are found in the primary target organs, such as the kidneys, joints, and salivary glands, as well as in the cardiovascular system. In animal models of rheumatic diseases, inflammation and tissue damage improve upon genetic or pharmacologic targeting of the inflammasome, supporting its pathogenic role. Herein, we review the clinicopathologic significance and therapeutic targeting of inflammasome activation in rheumatic diseases and related conditions based on recent findings.

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Macrophage Migration Inhibitory Factor Regulates U1 Small Nuclear RNP Immune Complex–Mediated Activation of the NLRP3 Inflammasome

Cited by 62 publications

References 56 publications

Soluble mediators in packed red blood cells augment lipopolysaccharide‐induced monocyte interleukin‐1β production

Soluble mediators in packed red blood cells augment lipopolysaccharide‐induced monocyte interleukin‐1β production

The Role of Macrophage Migration Inhibitory Factor in Alzheimer′s Disease: Conventionally Pathogenetic or Unconventionally Protective?

Advances in Disease Mechanisms and Translational Technologies: Clinicopathologic Significance of Inflammasome Activation in Autoimmune Diseases

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