Intracellular thiol redox status of macrophages directs the Th1 skewing in thioredoxin transgenic mice during aging

Murata, Yukie; Amao, Michiko; Yoneda, Junya; Hamuro, Junji

doi:10.1016/s0161-5890(01)00111-0

Cited by 71 publications

(52 citation statements)

References 47 publications

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“…A clearer understanding of the redox regulation of the AM phenotype could lead to improvements in the prevention and treatment of chronic inflammatory conditions. Several interesting studies have recently addressed the possibility that intracellular redox conditions may play a role in skewing the Th1/Th2 immune responses (7,17,18). This study is consistent with several of these findings.…”

Section: Discussionsupporting

confidence: 89%

Environmental oxygen tension affects phenotype in cultured bone marrow-derived macrophages

Pfau

Schneider

Archer

et al. 2004

American Journal of Physiology-Lung Cellular and Molecular Phys

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. Environmental oxygen tension affects phenotype in cultured bone marrow-derived macrophages. Am J Physiol Lung Cell Mol Physiol 286: L354-L362, 2004. First published October 3, 2003 10.1152/ajplung.00380.2002This study tested the hypothesis that the unique phenotype of alveolar macrophages (AM) is maintained through adaptation to the relatively high oxygen partial pressure (PO 2) of the lung, through modification of redox-sensitive transcription factors. BALB/c mouse bone marrowderived macrophages (BMC) were differentiated under different PO 2 and compared functionally to AM and peritoneal macrophages (PM). BMC differentiated in normoxia (PO 2 140 Torr, BMChigh) were similar to AM in having low phagocytic and antigen presenting cell (APC) activities. However, BMC grown in low oxygen tension as found in other tissues (Ͻ40 Torr, BMC low) were better phagocytes and APCs, similar to PM. BMC high were more oxidative intracellularly than BMC low, based on oxidation of dichlorofluorescein and higher glutathione disulfide/glutathione (GSH) ratios, despite having more GSH. Finally, lipopolysaccharide-induced nuclear factor-B translocation, measured by laser scanning cytometry, was reduced in BMC high and AM, compared with BMClow and PM, respectively. These data suggest that regulation of the AM phenotype may occur, at least in part, via inhibition of NF-B by the unique redox environment.redox; alveolar macrophage; glutathione; nuclear factor-B

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Section: Discussionsupporting

confidence: 89%

Environmental oxygen tension affects phenotype in cultured bone marrow-derived macrophages

Pfau

Schneider

Archer

et al. 2004

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…Exogenous administration of TRX to mice reduced airway inflammation in a mouse model of allergic asthma with concomitant increase in the levels of members of the IL-1 family in the lung, suggestive of reduced Th2 immunity by upregulating Th1-like cytokines, however, administration of TRX did not decrease allergen specific IgE production [23]. Murata et al reported that splenocytes from TRX-Tg mice produced increased ratio of Th1 cytokine production, and this was especially pronounced in older mice [29]. In vitro studies indicate that TRX augments Th1 immunity by promoting the production of IL-12 and IFN-g by monocytes and T cells, respectively [30,31].…”

Section: Discussionmentioning

confidence: 99%

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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“…Alterations in pulmonary thiol metabolism are widely recognized as a central feature of many chronic inflammatory lung diseases. Cellular thiol level has also been suggested as a key factor in Th1 and Th2 response patterns (47,48). That is, increased GSH/GSSH ratio (relatively reduced condition) directs Th1 skewing with elevation of IFN-g as naive Th0 cells differentiate preferentially to Th1 cells.…”

Section: Discussionmentioning

confidence: 99%

Antiviral Activity of Nrf2 in a Murine Model of Respiratory Syncytial Virus Disease

Cho

Imani

Miller-DeGraff

et al. 2009

Am J Respir Crit Care Med

171

170

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Rationale: Respiratory syncytial virus (RSV) is the most frequent cause of significant lower respiratory illness in infants and young children, but its pathogenesis is not fully understood. The transcription factor Nrf 2 protects lungs from oxidative injury and inflammation via antioxidant response element (ARE)-mediated gene induction. Objectives: The current study was designed to determine the role of Nrf 2-mediated cytoprotective mechanisms in murine airway RSV disease. Methods: Nrf 2-deficient (Nrf 2 2/2 ) and wild-type (Nrf 2 1/1 ) mice were intranasally instilled with RSV or vehicle. In a separate study, Nrf 2 1/1 and Nrf 2 2/2 mice were treated orally with sulforaphane (an Nrf 2-ARE inducer) or phosphate-buffered saline before RSV infection. Measurements and Main Results: RSV-induced bronchopulmonary inflammation, epithelial injury, and mucus cell metaplasia as well as nasal epithelial injury were significantly greater in Nrf 2 2/2 mice than in Nrf 2 1/1 mice. Compared with Nrf 2 1/1 mice, significantly attenuated viral clearance and IFN-g, body weight loss, heightened protein/ lipid oxidation, and AP-1/NF-kB activity along with suppressed antioxidant induction was found in Nrf 2 2/2 mice in response to RSV. Sulforaphane pretreatment significantly limited lung RSV replication and virus-induced inflammation in Nrf 2 1/1 but not in Nrf 2 2/2 mice. Conclusions: The results of this study support an association of oxidant stress with RSV pathogenesis and a key role for the Nrf 2-ARE pathway in host defense against RSV.

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Intracellular thiol redox status of macrophages directs the Th1 skewing in thioredoxin transgenic mice during aging

Cited by 71 publications

References 47 publications

Environmental oxygen tension affects phenotype in cultured bone marrow-derived macrophages

Environmental oxygen tension affects phenotype in cultured bone marrow-derived macrophages

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

Antiviral Activity of Nrf2 in a Murine Model of Respiratory Syncytial Virus Disease

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