INTERFERON-γ INHIBITION ATTENUATES LETHALITY AFTER CECAL LIGATION AND PUNCTURE IN RATS: IMPLICATION OF HIGH MOBILITY GROUP BOX-1

Yin, Kingsley; Gribbin, Elizabeth; Wang, Haichao

doi:10.1097/01.shk.0000175556.03300.c6

Cited by 53 publications

(51 citation statements)

References 32 publications

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“…This deleterious effect was also shown in the CLP model of polymicrobial peritonitis (92) and in a CLP model followed by a P. aeruginosa infection (93). Polymicrobial peritonitis performed in IFN-γ receptor-deficient mice (94) or in rats given anti-IFN-γ antibodies (95) led to the similar demonstration of this negative role. In mice injected with LPS, the ambiguous role of IFN-γ was demonstrated: IFN-γ protected against LPSinduced lung edema but acted in synergy with LPS to enhance the occurrence of death (96).…”

Section: Nk Cells As a Source Of Inflammatory Cytokines And Antimicromentioning

confidence: 65%

Natural Killer (NK) Cells in Antibacterial Innate Immunity: Angels or Devils?

Souza-Fonseca-Guimarães

Adib‐Conquy

Cavaillon

2011

Mol Med

136

125

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Natural killer (NK) cells were first described as immune leukocytes that could kill tumor cells and soon after were reported to kill virus-infected cells. In the mid-1980s, 10 years after their discovery, NK cells were also demonstrated to contribute to the fight against bacterial infection, particularly because of crosstalk with other leukocytes. A wide variety of immune cells are now recognized to interact with NK cells through the production of cytokines such as interleukin (IL)-2, IL-12, IL-15 and IL-18, which boost NK cell activities. The recent demonstration that NK cells express pattern recognition receptors, namely Toll-like and nucleotide oligomerization domain (NOD)-like receptors, led to the understanding that these cells are not only under the control of accessory cells, but can be directly involved in the antibacterial response thanks to their capacity to recognize pathogen-associated molecular patterns. Interferon (IFN)-γ is the predominant cytokine produced by activated NK cells. IFN-γ is a key contributor to antibacterial immune defense. However, in synergy with other inflammatory cytokines, IFN-γ can also lead to deleterious effects similar to those observed during sepsis. Accordingly, as the main source of IFN-γ in the early phase of infection, NK cells display both beneficial and deleterious effects, depending on the circumstances.

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Section: Nk Cells As a Source Of Inflammatory Cytokines And Antimicromentioning

confidence: 65%

Natural Killer (NK) Cells in Antibacterial Innate Immunity: Angels or Devils?

Souza-Fonseca-Guimarães

Adib‐Conquy

Cavaillon

2011

Mol Med

136

125

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“…Consistent with our findings, several studies demonstrated that IFN-γ has harmful effects on hosts with sepsis. Treatment with an anti-IFN-γ antibody significantly decreases mortality in the CLP-induced sepsis model [32], whereas the administration of recombinant IFN-γ significantly enhances it [33]. However, the mechanism by which IFN-γ promotes sepsis has been unclear.…”

Section: Discussionmentioning

confidence: 99%

IFN‐γ‐producing NKT cells exacerbate sepsis by enhancing C5a generation via IL‐10‐mediated inhibition of CD55 expression on neutrophils

Kim

Ahn

et al. 2014

Eur J Immunol

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A role for NKT cells has been implicated in sepsis, but the mechanism by which NKT cells contribute to sepsis remains unclear. Here, we examined WT and NKT-cell-deficient mice of C57BL/6 background during cecal ligation and puncture-induced sepsis. The levels of C5a, IFN-γ, and IL-10 were higher in the serum and peritoneal fluid of WT mice than in those of CD1d −/− mice, while the mortality rate was lower in CD1d −/− mice than in WT mice. C5a blockade decreased mortality of WT mice during sepsis, whereas it did not alter that of CD1d −/− mice. As assessed by intracellular staining, NKT cells expressed IFN-γ, while neutrophils expressed IL-10. Upon coculture, IL-10-deficient NKT cells enhanced IL-10 production by WT, but not IFN-γR-deficient, neutrophils. Meanwhile, CD1d −/− mice exhibited high CD55 expression on neutrophils during sepsis, whereas those cells from WT mice expressed minimal levels of CD55. Recombinant IL-10 administration into CD1d −/− mice reduced CD55 expression on neutrophils. Furthermore, adoptive transfer of sorted WT, but not IFN-γ-deficient, NKT cells into CD1d −/− mice suppressed CD55 expression on neutrophils, but increased IL-10 and C5a levels. Taken together, IFN-γ-producing NKT cells enhance C5a generation via IL-10-mediated inhibition of CD55 expression on neutrophils, thereby exacerbating sepsis.Keywords: C5a r IFN-γ r Neutrophils r NKT cell r Sepsis Additional supporting information may be found in the online version of this article at the publisher's web-site IntroductionNKT cells are a distinct T-cell subset characterized by the expression of natural killer receptors and semi-invariant TCRs. These cells recognize glycolipids presented by CD1d, an MHC class I-like Correspondence: Dr. Doo Hyun Chung e-mail: doohyun@snu.ac.kr protein expressed by APCs [1]. During bacterial infection, TCRs on NKT cells directly recognize glycolipids derived from certain Gramnegative bacterial membranes [2,3] and can be activated by innate cytokines secreted by dendritic cells that have been activated by microorganisms [2,4]. Furthermore, LPS-mediated engagement of TLR4 directly activates NKT cells in terms of differential * These authors contributed equally to this work. Eur. J. Immunol. 2014Immunol. . 44: 2025Immunol. -2035 cytokine production, thereby regulating immune diseases [5]. These findings suggest that NKT cells, activated during immune responses against bacteria, regulate bacteria-mediated pathologic processes such as sepsis. Sepsis is a complex inflammatory dysregulation that causes multiple organ dysfunction and coagulopathy, often resulting in death [6,7]. Several studies have demonstrated that NKT cells promote LPS-or cecal ligation and puncture (CLP)-induced sepsis in mice through the production of . Consistent with these findings, two independent studies have demonstrated that treatment of C57BL/6 mice with anti-CD1d antibody enhances survival rates during CLP-induced sepsis [11,12], suggesting that NKT-cell-mediated promotion of sepsis depends on an interaction between CD1d and TCR...

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“…An increasing number of agents (ethyl pyruvate, stearoyl lysophosphatidylcholine, nicotine) dose-dependently inhibits HMGB1 release, and confers significant protection against lethal sepsis [2,8,[35][36][37][38]. Neutralizing antibodies against IFN-γ, a cytokine capable of stimulating HMGB1 release [10], significantly reduced circulating HMGB1 levels in septic rats, and consequently rescued rats from lethal sepsis [39]. Most recently, we discovered that green tea and aqueous extract of a Chinese herb, Angelica sinesis, significantly attenuated endotoxin-induced HMGB1 release [40,41], and rescued mice from lethal sepsis [41].…”

Section: Suppression Of Hmgb1 Release -The Caging Of the Beastmentioning

confidence: 99%

Role of HMGB1 in cardiovascular diseases

Sama

Wang

2006

Current Opinion in Pharmacology

111

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A nuclear protein, high mobility group box 1 (HMGB1), is released passively by necrotic cells, and actively by macrophages/monocytes in response to exogenous and endogenous inflammatory stimuli. After binding to the receptor for advanced glycation end products (RAGE) or toll-like receptor 4 (TLR4), HMGB1 activates vascular endothelial cells and macrophages/monocytes to express proinflammatory cytokines, chemokines and adhesion molecules. Pharmacological suppression of its activities or release is protective against lethal endotoxemia and sepsis, establishing HMGB1 as a critical mediator of lethal systemic inflammation. In light of the pathogenic role of inflammation in cardiovascular diseases, we propose that HMGB1, a proinflammatory cytokine derived from both injured endothelium and activated macrophages/monocytes, could contribute to the progression of atherosclerosis and other cardiovascular diseases.

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INTERFERON-γ INHIBITION ATTENUATES LETHALITY AFTER CECAL LIGATION AND PUNCTURE IN RATS: IMPLICATION OF HIGH MOBILITY GROUP BOX-1

Cited by 53 publications

References 32 publications

Natural Killer (NK) Cells in Antibacterial Innate Immunity: Angels or Devils?

Natural Killer (NK) Cells in Antibacterial Innate Immunity: Angels or Devils?

IFN‐γ‐producing NKT cells exacerbate sepsis by enhancing C5a generation via IL‐10‐mediated inhibition of CD55 expression on neutrophils

Role of HMGB1 in cardiovascular diseases

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