The Transcription Factor Nuclear Factor of Activated T Cells c3 Modulates the Function of Macrophages in Sepsis

Ranjan, Ravi; Deng, Jing; Chung, Sangwoon; Lee, Yong Gyu; Park, Gye Young; Xiao, Lei; Joo, Myungsoo; Christman, John W.; Karpurapu, Manjula

doi:10.1159/000362647

Cited by 29 publications

(38 citation statements)

References 38 publications

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“…Macrophages were pretreated with hemozoin and stimulated with - IFNγ [100 ng/ml] (BD Pharmingen), LPS [1 μg/ml] (Alexis Biochemicals) and IL4 [20 ng/ml] (RnD Systems), and processed for Western immunoblotting for iNOS as described previously [19]. …”

Section: Methodsmentioning

confidence: 99%

Hemozoin Regulates iNOS Expression by Modulating the Transcription Factor NF-kB in Macrophages

et al. 2016

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Hemozoin (Hz) is released from ruptured erythrocytes during malaria infection caused by Plasmodium sp., in addition the malaria infected individuals are prone to bacterial sepsis. The molecular interactions between Hz, bacterial components and macrophages remains poorly investigated. In this report, we investigated the combinatorial immune-modulatory effects of phagocytosed Hz, Interferon gamma (IFNγ) or lipopolysaccharide (LPS) in macrophages. Macrophages were treated with various concentrations of commercial synthetic Hz, and surprisingly it did not result in inducible nitric oxide synthase (iNOS) expression. However, when macrophages were pretreated with Hz and then challenged with IFNγ or LPS, there was a differential impact on iNOS expression. There was an increase in iNOS expression when macrophages were pre-treated with Hz and subsequently treated with IFNγ when compared to IFNγ alone. Whereas iNOS expression was reduced when Hz phagocytosed macrophages were stimulated with LPS compared to LPS alone. Furthermore, there was an increased activation of NF-κB in Hz phagocytosed macrophages that were challenged with IFNγ. The interaction between Hz and macrophages has an impact on iNOS expression.

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Section: Methodsmentioning

confidence: 99%

Hemozoin Regulates iNOS Expression by Modulating the Transcription Factor NF-kB in Macrophages

et al. 2016

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“…Evidence shows that CsA blocks NFAT binding to the inducible NO synthase (iNOS) promoter, causing a reduction of iNOS expression and nitrite production in macrophages (14,15). CsA can also down-regulate the enzyme cyclooxygenase-2 (COX-2) in the kidney, which converts arachidonic acid into prostaglandin E2 (PGE2), an inflammatory mediator that modulates vascular permeability to expedite immune cell recruitment (16,17).…”

Section: Calcineurin Inhibitorsmentioning

confidence: 99%

Effects of Antirejection Drugs on Innate Immune Cells After Kidney Transplantation

et al. 2019

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Over the last decades, our understanding of adaptive immune responses to solid organ transplantation increased considerably and allowed development of immunosuppressive drugs targeting key alloreactive T cells mechanism. As a result, rates of acute rejection dropped and short-term graft survival improved significantly. However, long-term outcomes are still disappointing. Recently, increasing evidence supports that innate immune responses plays roles in allograft rejection and represents a valuable target to further improve long-term allograft survival. Innate immune cells are activated by molecules with stereotypical motifs produced during injury (i.e., damage-associated molecular patterns, DAMPS) or infection (i.e., pathogen-associated molecular patterns, PAMPs). Activated innate immune cells can exert direct pro-and anti-inflammatory effects, while also priming adaptive immune responses. These cells are activated after transplantation by multiple stimuli, including ischemia-reperfusion injury, rejection, and infections. Data from animal models of graft rejection, show that inhibition of innate immunity promotes development of tolerance. Therefore, understanding mechanisms of innate immunity is important to improve graft outcomes. This review discusses effects of currently used immunosuppressive agents on innate immune responses in kidney transplantation.

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“…The inhibition of nFaT was revealed to be an effective method for reducing the multiple inflammatory cytokines induced by TnF-α in human retinal microvascular endothelial cells (16), thus further highlighting nFaT signaling as a potential anti-inflammatory target. Recent studies (17,18) have revealed that NFATc3 is a key molecular regulator of sepsis-induced lung injury. notably, nFaTc4 has been suggested to be a pivotal regulatory event in endothelial cell inflammation (15), which is an early step in the development of lung injury.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of calcineurin/NFATc4 signaling attenuates ventilator‑induced lung injury

Fang

Liu

et al. 2019

Mol Med Report

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Ventilator-induced lung injury (Vili) is a life-threatening condition caused by the inappropriate use of mechanical ventilation (MV). However, the precise molecular mechanism inducing the development of Vili remains to be elucidated. in the present study, it was revealed that the calcineurin/nFaTc4 signaling pathway mediates the expression of adhesion molecules and proinflammatory cytokines essential for the development of Vili. The present results revealed that a high tidal volume ventilation (HV) caused lung inflammation and edema in the alveolar walls and the infiltration of inflammatory cells. The calcineurin activity and protein expression in the lungs were increased in animals with Vili, and nFaTc4 translocated into the nucleus following calcineurin activation. Furthermore, the translocation of nFaTc4 and lung injury were prevented by a calcineurin inhibitor (csa). Thus, the present results highlighted the critical role of the calcineurin/nFaTc4 signaling pathway in Vili and suggest that this pathway coincides with the release of icaM-1, VcaM-1, TnF-α and il-1β.

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The Transcription Factor Nuclear Factor of Activated T Cells c3 Modulates the Function of Macrophages in Sepsis

Cited by 29 publications

References 38 publications

Hemozoin Regulates iNOS Expression by Modulating the Transcription Factor NF-kB in Macrophages

Hemozoin Regulates iNOS Expression by Modulating the Transcription Factor NF-kB in Macrophages

Effects of Antirejection Drugs on Innate Immune Cells After Kidney Transplantation

Inhibition of calcineurin/NFATc4 signaling attenuates ventilator‑induced lung injury

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