Lipopolysaccharide: Neutralization by Polymyxin B Shuts Down the Signaling Pathway of Nuclear Factor κB in Peripheral Blood Mononuclear Cells, Even during Activation

Tsuzuki, Hideyuki; Tani, Tohru; Ueyama, Hisao; Kodama, Masashi

doi:10.1006/jsre.2001.6227

Cited by 75 publications

(56 citation statements)

References 23 publications

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“…Polymyxin B (PMX) has long been known to neutralize the various biological activities of endotoxins 50. In 1990, after the biocompatibility of sterilized PMX‐F (polymyxin B covalently immobilized on fibers) was demonstrated, the Critical Network Group in Japan obtained permission from the Japanese Ministry of Health and Welfare to clinically test hemoperfusion with PMX‐F, and subsequently reported that it was safe and effective for patients with septic shock 51, 52.…”

Section: Immunological Modification Therapiesmentioning

confidence: 99%

Mechanisms of sepsis‐induced immunosuppression and immunological modification therapies for sepsis

Ono

Tsujimoto

Hiraki

et al. 2018

Annals of Gastroent Surgery

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Surgical injury can be a life‐threatening complication, not only due to the injury itself, but also due to immune responses to the injury and subsequent development of infections, which readily result in sepsis. Sepsis remains the leading cause of death in most intensive care units. Unfavorable outcomes of several high‐profile trials in the treatment of sepsis have led researchers to state that sepsis studies need a new direction. The immune response that occurs during sepsis is characterized by a cytokine‐mediated hyper‐inflammatory phase, which most patients survive, and a subsequent immunosuppressive phase. Therefore, therapies that improve host immunity might increase the survival of patients with sepsis. Many mechanisms are responsible for sepsis‐induced immunosuppression, including apoptosis of immune cells, increased regulatory T cells and expression of programmed cell death 1 on CD4+ T cells, and cellular exhaustion. Immunomodulatory molecules that were recently identified include interleukin‐7, interleukin‐15, and anti‐programmed cell death 1. Recent studies suggest that immunoadjuvant therapy is the next major advance in sepsis treatment.

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Section: Immunological Modification Therapiesmentioning

confidence: 99%

Mechanisms of sepsis‐induced immunosuppression and immunological modification therapies for sepsis

Ono

Tsujimoto

Hiraki

et al. 2018

Annals of Gastroent Surgery

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“…In some experiments aimed at blocking secreted IFN-γ, anti-IFN-γ neutralizing antibodies (monoclonal IgG1, 1 μg/ml; Diaclone) were added to the culture medium, together with anti-IL-10 antibodies, for 48 h. In some experiments aimed at blocking the biological activity of TGF-βs, mucosa explant cultures were incubated with anti-TGF-βRII neutralizing antibodies (polyclonal goat antibody, 5 μg/ml; R&D Systems) or with normal goat serum (control cultures). Some experiments were performed in the presence of polymyxin B (SigmaAldrich), a neutralizing agent of bacterial LPS (49,50). In such experiments, dissected fragments were subjected to 3 10-min washes with the culture medium containing 30 μg/ml polymyxin B on a rocking platform.…”

Section: Figurementioning

confidence: 99%

Mucosal IL-10 and TGF-β play crucial roles in preventing LPS-driven, IFN-γ–mediated epithelial damage in human colon explants

Jarry¹,

Bossard²,

Bou-Hanna³

et al. 2008

J. Clin. Invest.

106

123

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IL-10 is an immunomodulatory cytokine that plays an obligate role in preventing spontaneous enterocolitis in mice. However, little is known about IL-10 function in the human intestinal mucosa. We showed here that IL-10 was constitutively expressed and secreted by the human normal colonic mucosa, including epithelial cells. Depletion of IL-10 in mucosal explants induced both downregulation of the IL-10-inducible, immunosuppressive gene BCL3 and upregulation of IFN-γ, TNF-α, and IL-17. Interestingly, TGF-β blockade also strongly induced IFN-γ production. In addition, the high levels of IFN-γ produced upon IL-10 depletion were responsible for surface epithelium damage and crypt loss, mainly by apoptosis. Polymyxin B, used as a scavenger of endogenous LPS, abolished both IFN-γ production and epithelial barrier disruption. Finally, adding a commensal bacteria strain to mucosa explant cultures depleted of both IL-10 and LPS reproduced the ability of endogenous LPS to induce IFN-γ secretion. These findings demonstrate that IL-10 ablation leads to an endogenous IFN-γ-mediated inflammatory response via LPS from commensal bacteria in the human colonic mucosa. We also found that both IL-10 and TGF-β play crucial roles in maintaining human colonic mucosa homeostasis.

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“…2. When LPS was added in combination with polymyxin B, a molecule that is known to bind LPS and neutralize its effects (44), there was no up-regulation of IRF-7 in the PDC (Fig. 4F).…”

Section: Purified Lps Up-regulates Irf-7 Expression In Pdc and Is Inmentioning

confidence: 99%

Regulation of IFN Regulatory Factor-7 and IFN-α Production by Enveloped Virus and Lipopolysaccharide in Human Plasmacytoid Dendritic Cells

Dai

Megjugorac²,

Amrute

et al. 2004

The Journal of Immunology

134

117

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Human plasmacytoid dendritic cells (PDC) are a major source of IFN-α upon exposure to enveloped viruses and TLR-7 and TLR-9 ligands. Although IFN regulatory factor-7 (IRF-7) is known to play an essential role in virus-activated transcription of IFN-α genes, the molecular mechanisms of IFN-α production in human PDC remain poorly understood. We and others have recently reported high constitutive levels of IRF-7 expression in PDC as compared with other PBMC. In this study, we demonstrate that both LPS and HSV up-regulate the expression of IRF-7 in PDC, and that this enhancement of IRF-7 is dependent on NF-κB activation. The NF-κB inhibitors MG132 and pyrrolidinedithiocarbamate efficiently inhibited the induction of IRF-7 by HSV or LPS, and also down-regulated the constitutive expression of IRF-7 in PDC and blocked the HSV-induced production of IFN-α. In addition, we found that nuclear translocation of IRF-7 occurred rapidly in response to HSV stimulation, but not in response to LPS, which is consistent with the stimulation of IFN-α production by virus and not by LPS. Although LPS by itself was not able to induce IFN-α production, it led to rapid up-regulation of TLR-4 on PDC and increased the magnitude and accelerated the kinetics of HSV-induced IFN-α production in PDC, providing a mechanism that might be operative in a scenario of mixed infection. In contrast to the current concept of IFN-α regulation established in cell lines, this study strongly supports the immediate availability of high constitutive levels of IRF-7 expression in PDC, and suggests an activation required for IRF-7 that contributes to IFN-α production in virus-stimulated PDC.

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Lipopolysaccharide: Neutralization by Polymyxin B Shuts Down the Signaling Pathway of Nuclear Factor κB in Peripheral Blood Mononuclear Cells, Even during Activation

Cited by 75 publications

References 23 publications

Mechanisms of sepsis‐induced immunosuppression and immunological modification therapies for sepsis

Mechanisms of sepsis‐induced immunosuppression and immunological modification therapies for sepsis

Mucosal IL-10 and TGF-β play crucial roles in preventing LPS-driven, IFN-γ–mediated epithelial damage in human colon explants

Regulation of IFN Regulatory Factor-7 and IFN-α Production by Enveloped Virus and Lipopolysaccharide in Human Plasmacytoid Dendritic Cells

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