Thioredoxin, a Redox Enzyme Released in Infection and Inflammation, Is a Unique Chemoattractant for Neutrophils, Monocytes, and T Cells

Bertini, Riccardo; Howard, O. M. Zack; Dong, Huifang; Oppenheim, Joost J.; Bizzarri, Cinzia; Sergi, Rita; Caselli, Gianfranco; Pagliei, Sabrina; Romines, Brie; Wilshire, Jennifer A.; Mengozzi, Manuela; Nakamura, Hajime; Yodoi, Junji; Pekkari, Klas; Gurunath, Ramanathan; Holmgren, Arne; Herzenberg, Leonore A.; Herzenberg, Leonard A.; Ghezzi, Pietro

doi:10.1084/jem.189.11.1783

Cited by 297 publications

(213 citation statements)

References 47 publications

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“…In contrast, the serum level of KC, the murine homologue of human IL-8, was increased in the TRX group compared with the control group. Consistent with this finding, Bertini et al [38] reported that TRX per se was chemotactic for monocytes, polymorphonuclear leukocytes, and T lymphocytes. This may partially explain why no beneficial effects of TRX were seen in some of the TRX-treated mice.…”

Section: Discussionsupporting

confidence: 72%

Thioredoxin-1 Attenuates Early Graft Loss after Intraportal Islet Transplantation in Mice

Asami

Inagaki

Imura

et al. 2012

Transplantation Journal

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Aims: Recent studies suggest that decreasing oxidative stress is crucial to achieve successful islet transplantation. Thioredoxin-1 (TRX), which is a multifunctional redox-active protein, has been reported to suppress oxidative stress. Furthermore, it also has anti-inflammatory and anti-apoptotic effects. In this study, we investigated the effects of TRX on early graft loss after islet transplantation.Methods: Intraportal islet transplantation was performed for two groups of streptozotocin-induced diabetic mice: a control and a TRX group. In addition, TRX-transgenic (Tg) mice were alternately used as islet donors or recipients.Results: The changes in blood glucose levels were significantly lower in the TRX group compared with the TRX-Tg donor and control groups (p,0.01). Glucose tolerance and the residual graft mass were considerably better in the TRX group. TRX significantly suppressed the serum levels of interleukin-1b (p,0.05), although neither anti-apoptotic nor anti-chemotactic effects were observed. Notably, no increase in the 8-hydroxy-29-deoxyguanosine level was observed after islet infusion, irrespective of TRX administration. Conclusions:The present study demonstrates that overexpression of TRX on the islet grafts is not sufficient to improve engraftment. In contrast, TRX administration to the recipients exerts protective effects on transplanted islet grafts by suppressing the serum levels of interleukin-1b. However, TRX alone appears to be insufficient to completely prevent early graft loss after islet transplantation. We therefore propose that a combination of TRX and other anti-inflammatory treatments represents a promising regimen for improving the efficacy of islet transplantation.

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Section: Discussionsupporting

confidence: 72%

Thioredoxin-1 Attenuates Early Graft Loss after Intraportal Islet Transplantation in Mice

Asami

Inagaki

Imura

et al. 2012

Transplantation Journal

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“…Thioredoxin is a ubiquitous intracellular enzyme with antioxidant activity 41 . Both galectins [42][43][44] and thioredoxin 45,46 have been shown to stimulate various leukocytes and endothelium ex vivo and when injected in vivo to stimulate inflammation. To what extent these molecules actually contribute to the deathinduced inflammatory response, if at all, is unknown.…”

Section: Intracellular Damps With Proinflammatory Activitymentioning

confidence: 99%

How dying cells alert the immune system to danger

2008

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When a cell dies in vivo the event does not go unnoticed. The host has evolved mechanisms to detect the death of cells and rapidly investigate the nature of their demise. If cell death is a result of natural causes, that is, it is part of normal physiological processes, then there is little threat to the organism. In this situation, little else is done other than removing the corpse. However, if cells have died as the consequence of some violence or disease, then both defence and repair mechanisms are mobilized. The importance of this process to host defence and disease pathogenesis has only been appreciated relatively recently. This article will review our current knowledge of these processes.The immune system was recognized in ancient times and rediscovered by Jenner and Pasteur based on its ability to confer protection upon repeat exposure to a pathogen. Through subsequent studies by Von Behring and others it rapidly became apparent that the immune system had the potential to respond not only to whole microorganisms, but to virtually any molecule that was "foreign" to the host. However, whereas injection of such molecules would often provoke a robust immune response, this did not invariably occur. Immunization protocols improved in the 1920s with the discovery by Ramon and Glenny of immunostimulatory molecules (adjuvants [G]) that could boost immune responses to co-administered antigens. Adjuvants were typically of microbial origin and became widely used to promote the effectiveness of immunizations. In the 1960s, Dresser showed that a foreign protein when highly purified would only elicit an immune response if it was admixed with a microbial adjuvant 1 . Injected by itself, the antigen not only failed to elicit immunity but actually induced a state of tolerance 2 . However, the significance of these observations was not well appreciated and adjuvants remained one of those things that everyone used because they were part of standard operating procedures.In 1989 Janeway put these empirical observations into a conceptual framework 3 (Fig. 1). He proposed that the immune system did not respond to all foreign antigens but only to those that are potentially associated with infection. The underlying idea here was that the immune system evolved to protect organisms against microorganisms and this discrimination between infectious versus noninfectious antigens focused defences on real threats rather than innocuous situations.At this time, it was already recognized that in order to stimulate T cell responses, antigens had to first be acquired and presented on MHC molecules of an antigen presenting cell (APC). Moreover, it was further known that APCs also provided additional costimulatory signals necessary to activate T cells. Janeway incorporated these principles into his model (Fig. 1). He postulated that the discrimination between infectious and noninfectious non-self molecules was made by the APCs of the innate immune system through receptors that would recognize pathogen-associated molecular patterns (PAMP...

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“…Circulating levels of Trx were reported to be increased in patients with heart disease, rheumatoid arthritis, acute lung injury, or HIV infection, and showed various associations with severity of disease [92][93][94][95]. Extracellular Trx can act as a unique chemoattractant for neutrophils, monocytes, and T cells [96]. A 10-kDa C-terminally truncated variant of Trx (termed Trx80) is also secreted and present in plasma, and acts as a potent mitogenic cytokine that stimulates growth of resting human peripheral blood mononuclear cells [95], and differentiation of human CD14(+) monocytes into a novel phenotype in association with activation of mitogen activated protein kinases [97].…”

Section: Biochemical and Genetic Regulation Of Reversible Cysteine Oxmentioning

confidence: 99%

Redox-based regulation of signal transduction: Principles, pitfalls, and promises

Janssen–Heininger¹,

Mossman²,

Heintz³

et al. 2008

Free Radical Biology and Medicine

688

652

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Thioredoxin, a Redox Enzyme Released in Infection and Inflammation, Is a Unique Chemoattractant for Neutrophils, Monocytes, and T Cells

Cited by 297 publications

References 47 publications

Thioredoxin-1 Attenuates Early Graft Loss after Intraportal Islet Transplantation in Mice

Thioredoxin-1 Attenuates Early Graft Loss after Intraportal Islet Transplantation in Mice

How dying cells alert the immune system to danger

Redox-based regulation of signal transduction: Principles, pitfalls, and promises

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