Role for macrophage migration inhibitory factor in asthma

Mizue, Yuka; Ghani, Samina; Leng, Lin; McDonald, Courtney; Kong, Philip; Baugh, John; Lane, Stephen; Craft, Joseph; Nishihira, Jun; Donnelly, Seamas C.; Zhu, Zhou; Bucala, Richard

doi:10.1073/pnas.0507189102

Cited by 193 publications

(228 citation statements)

References 38 publications

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“…Consistent with this data, MIF levels were significantly lower in colonic tissue and sera in TRX-Tg mice in a mouse model of acute DSS-induced colitis [32]. Recent studies indicate that MIF plays an essential role in the pathogenesis of allergic airway inflammation [3][4][5][6]. Upon allergen sensitization and challenge, mice lacking MIF exhibit reduced AHR, tissue eosinophilia, and mucus metaplasia with concomitant decreases in levels of eotaxin and IL-13 in BALF.…”

Section: Discussionsupporting

confidence: 73%

“…Recent studies suggest that MIF may play a key role in the pathogenesis of airway inflammation [3][4][5][6]. Therefore, we next examined the lungs of TRX-Tg and WT mice for differences in MIF expression in our model of asthma.…”

Section: Reduced Production Of Mif By Lung Epithelial Cells From Trx-mentioning

confidence: 99%

“…Although eosinophils are the predominant cell type in the lung of asthmatic subjects that mediate tissue damage, allergen specific Th2 cells generated in the secondary lymphoid organs and migrated into the lung are central to the pathogenesis of asthma via secretion of IL-4 and IL-5 contributing to mobilization of eosinophils and IL-9 and IL-13 contributing to AHR [2]. Additionally, recent studies have implicated MIF produced by lung epithelial cells, macrophages, and mast cells as an essential factor in the pathogenesis of asthma [3][4][5][6].…”

Section: Introductionmentioning

confidence: 99%

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Thioredoxin suppresses airway inflammation independently of systemic Th1/Th2 immune modulation

Torii

Wang

et al. 2010

Eur J Immunol

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Oxidative stress plays an important role in the pathogenesis of asthma via the upregulation of local inflammatory mediators and/or promoting Th2-skewing during Ag sensitization. Thioredoxin (TRX), a 12 kDa redox-active protein with antioxidative property, has been recently shown to play a protective role in various inflammatory diseases. Using a mouse model of asthma, we show here that IL-13 and eotaxin production are decreased in TRX-Tg mice leading to reduced eosinophils recruitment and mucus metaplasia. The reduction in airway inflammation occurs without the attenuation of systemic Th2 immunity in that comparable levels of Th2-type cytokines and Ig were detected in LN and serum, respectively, from TRX-Tg and WT mice. Likewise, CD4 1 T cells from both strains of mice developed similar Th1 and Th2 responses in vitro. Asthmatic lungs of TRX-Tg and WT mice contained similar amounts of GATA-3 1 and Foxp3 1 T cells. Finally, production of MIF, an upstream modulator of airway inflammation, was significantly reduced in the lungs of TRX-Tg mice. Our data suggest that TRX suppresses airway inflammation by inhibiting MIF production thereby limiting the downstream recruitment of eosinophils to the lung independently of modulating systemic Th1/Th2 immunity.

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Section: Discussionsupporting

confidence: 73%

Section: Reduced Production Of Mif By Lung Epithelial Cells From Trx-mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Thioredoxin suppresses airway inflammation independently of systemic Th1/Th2 immune modulation

Torii

Wang

et al. 2010

Eur J Immunol

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“…Previous studies have shown that MIF regulates the activation of T cells induced by mitogenic or antigenic stimuli, inducing IL-2 secretion and lymphocyte proliferation [31,34]. In fact, MIF -/-mice have a reduced spleen T cell-proliferative response upon OVA restimulation [34]. We also observed that restimulation of spleen cells with OVA caused a reduced proliferative response and IL-13 production in allergensensitized and challenged MIF -/-mice compared to WT mice (Fig.…”

Section: Involvement Of Mif On Antigen-specific Responsessupporting

confidence: 56%

“…A recent study demonstrated that MIF -/-mice lack the cardinal features of asthma and display a reduction of IL-4, IL-5 and eotaxin amounts in the lung 16 h after the last challenge [34]. Considering the essential role of Th2 cytokines in eosinophilic inflammation, mucus metaplasia and AHR, and the lack of these features in MIF -/-mice, we measured the concentrations of IL-4, IL-5 and IL-13 in the BALF 6 h after the last challenge.…”

Section: Mif Regulates Production Of Inflammatory Mediators In the Almentioning

confidence: 99%

Macrophage migration inhibitory factor is essential for allergic asthma but not for Th2 differentiation

et al. 2007

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Macrophage migration inhibitory factor (MIF) is increased in asthmatic patients and plays a critical role in the pathogenesis of asthma. We show here that mice lacking MIF failed to develop airway hyper-responsiveness (AHR), tissue eosinophilia, and mucus metaplasia. Analysis of the bronchoalveolar fluids revealed a substantial reduction of IL-13, eotaxin and cysteinyl-leukotrienes. The lack of these cardinal features of asthma in MIF -/-mice occurs regardless of high concentrations of IL-4 in the lung and OVAspecific IgE in the serum. Antigen-specific lymphocyte proliferation and IL-13 production were similarly increased in the draining lymph nodes of OVA-immunized and challenged MIF -/-mice compared to WT, but were reduced in the spleen of MIF -/-, thus indicating differential roles of MIF in these compartments. Stimulation of naive CD4 + cells with anti-CD3 antibody demonstrated that MIF -/-cells produced increased amounts of IFN-c and IL-4 compared to WT CD4 + cells. Finally, treatment of sensitized BALB/c mice with neutralizing anti-MIF antibody abrogated the development of ARH and airway inflammation without affecting the production of Th2 cytokines or IgE. The present study demonstrates that MIF is required for allergic inflammation, adding important elements to our knowledge of asthma pathogenesis and suggesting that neutralization of MIF might be of therapeutic value in asthma. IntroductionAllergic asthma is a disorder characterized by chronic lung inflammation, reversible airway obstruction and increases in airway hyper-responsiveness (AHR) to nonspecific stimuli. Several studies have provided compelling evidences that the lung infiltrating leukocytes and the proinflammatory mediators they produce initiate cellular damage, amplify the immune response, cause airway physiological changes and tissue remodeling [1]. The airway inflammation of asthma has a predominance of Th2 CD4 + lymphocytes, eosinophils and mast cells infiltrating the lung interstitium. Several studies indicate the existence of a mechanism dependent on IL-5 and eosinophils that induce pulmonary damage and intensify AHR [3][4][5]. In other studies, however, the induction of AHR was observed despite the absence of infiltrating eosinophils, suggesting dissociation between these phenomena [6][7][8][9][10]. Macrophage migration inhibitory factor (MIF) is a pleiotropic molecule and critical mediator of innate and acquired immune responses [11,12]. Pre-formed MIF protein is present in many cell types and is released in response to different stimuli, such as infection and cytokine stimulation [12]. MIF exhibits several proinflammatory functions, including the induction of TNF-a, IL-1 and NO release from macrophages, and the production of arachidonic acid and eicosanoids through the induction of phospholipase A 2 and cyclooxygenase [13,14]. A unique property of MIF is its secretion by immune cells in response to physiological increase in glucocorticoid levels. Once released, MIF can counterregulate the anti-inflammatory effects of steroids on cyt...

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Investigation of short range ordering in PES/PEES alternative copolymer by means of radial distribution functions derived from X‐ray diffraction

Zhou

Jiang

2007

J of Applied Polymer Sci

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Two samples of poly(ether sulfone)/poly (ether ether sulfone) alternative copolymer, showing marked differences in tensile behavior due to different thermal histories, were investigated by radial distribution function (RDF) methods. The RDF patterns were virtually identical and showed that the short range order (0-14 Å ) in the samples had been essentially unaffected by the annealing procedures. Two intramolecular distances in the polymer repeat unit were successfully resolved in the RDF pattern. However, there were only suggestions of broad peaks at r ¼ 5.5 Å and r ¼ 11 Å attributable to intermolecular ordering, indicating that little intermolecular ordering had occurred in either sample. The appearance of two peaks at $ 5 Å periodic suggested the existence of more or less parallel chain segments in the copolymers. Explanations of the different tensile properties of the two samples which assume a significant short range reordering on annealing are thus ruled out on the available evidence. A more highly annealed sample was examined to assess the sensitivity of the RDF method to short range intermolecular ordering. The RDF plot of this sample showed a marked periodicity peaking at intervals of $ 5 Å which was attributed to intermolecular ordering, thus confirming the above conclusion.

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Role for macrophage migration inhibitory factor in asthma

Cited by 193 publications

References 38 publications

Thioredoxin suppresses airway inflammation independently of systemic Th1/Th2 immune modulation

Thioredoxin suppresses airway inflammation independently of systemic Th1/Th2 immune modulation

Macrophage migration inhibitory factor is essential for allergic asthma but not for Th2 differentiation

Investigation of short range ordering in PES/PEES alternative copolymer by means of radial distribution functions derived from X‐ray diffraction

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