Nystatin Induces Secretion of Interleukin (IL)-1β, IL-8, and Tumor Necrosis Factor Alpha by a Toll-Like Receptor-Dependent Mechanism

Razonable, Raymund R.; Hénault, Martin; Watson, Harold L.; Payá, Carlos V.

doi:10.1128/aac.49.8.3546-3549.2005

Cited by 31 publications

(21 citation statements)

References 17 publications

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“…8). This level of inhibition is comparable to that found in at least two other studies where this mAb was used (32,33). The fact that the epitope for GD2.F4 maps to the outer loop of LRR11 confirms the importance of this region in receptor function.…”

Section: Discussionsupporting

confidence: 73%

The Polymorphism P315L of Human Toll-Like Receptor 1 Impairs Innate Immune Sensing of Microbial Cell Wall Components

Omueti

Mazur²,

Thompson³

et al. 2007

The Journal of Immunology

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As a pattern recognition receptor, TLR1 mediates innate immune responses to a variety of microbial cell wall components including bacterial lipoproteins. We have previously shown that the central region of the extracellular domain of human TLR1, comprising leucine-rich repeat (LRR) motifs 9–12, is required for the sensing of bacterial lipopeptides. In this study, we have investigated three nonsynonymous single nucleotide polymorphisms (SNPs) located in this region of TLR1 by generating these variants and examining receptor function. We have found that a variant of TLR1 based upon the SNP P315L, located in the loop of LRR motif 11 (LRR11), is greatly impaired in mediating responses to lipopeptides and a variety of other bacterial agonists for this receptor. Despite normal cell surface expression, the P315L variant also fails to bind to GD2.F4, a commonly used anti-TLR1 mAb. Although a number of amino acid substitutions at position 315 impair receptor function, the leucine substitution has the strongest deleterious effect. GD2.F4 inhibits agonist-induced activation of TLR1, supporting a crucial role for the loop of LRR11 in receptor function. These results also suggest that the P315L SNP may predispose certain individuals to infectious diseases for which the sensing of microbial cell components by TLR1 is critical to innate immune defense.

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Section: Discussionsupporting

confidence: 73%

The Polymorphism P315L of Human Toll-Like Receptor 1 Impairs Innate Immune Sensing of Microbial Cell Wall Components

Omueti

Mazur²,

Thompson³

et al. 2007

The Journal of Immunology

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“…Nystatin was previously reported to induce pro-inflammatory cytokines via TLR1/TLR2 signaling [3] but we found that nystatin, as well as amphotericin B and natamycin, required LPS prestimulation to induce pro-IL-1β as a prerequisite for IL-1β secretion. Hence, or data argue against a direct agonistic role of these drugs on TLRs.…”

Section: Discussionmentioning

confidence: 60%

Polyene Macrolide Antifungal Drugs Trigger Interleukin-1β Secretion by Activating the NLRP3 Inflammasome

Darisipudi¹,

Allam

Rupanagudi³

et al. 2011

PLoS ONE

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The use of antimycotic drugs in fungal infections is based on the concept that they suppress fungal growth by a direct killing effect. However, amphotericin and nystatin have been reported to also trigger interleukin-1β (IL-1β) secretion in monocytes but the molecular mechanism is unknown. Here we report that only the polyene macrolides amphotericin B, nystatin, and natamycin but none of the tested azole antimycotic drugs induce significant IL-1β secretion in-vitro in dendritic cells isolated from C57BL/6 mouse bone marrow. IL-1β release depended on Toll-like receptor-mediated induction of pro-IL-1β as well as the NLRP3 inflammasome, its adaptor ASC, and caspase-1 for enzymatic cleavage of pro-IL-1β into its mature form. All three drugs induced potassium efflux from the cells as a known mechanism for NLRP3 activation but the P2X7 receptor was not required for this process. Natamycin-induced IL-1β secretion also involved phagocytosis, as cathepsin activation as described for crystal-induced IL-1β release. Together, the polyene macrolides amphotericin B, nystatin, and natamycin trigger IL-1β secretion by causing potassium efflux from which activates the NLRP3-ASC-caspase-1. We conclude that beyond their effects on fungal growth, these antifungal drugs directly activate the host's innate immunity.

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“…The nystatin model of paw edema induces chronic inflammation, which can last up to 15 days [199]. Nystatin triggers TLR-2 and induces secretion of TNF-α, IL-8, and IL-1β [200]. Based on more recent data from our laboratory [20], we would suggest that the reduced inflammation in this model was the result of creatine reducing expression of TLR-2 in vivo .…”

Section: Creatine As An Anti-inflammatory Agentmentioning

confidence: 99%

Beyond muscles: The untapped potential of creatine

Riesberg

Weed

McDonald

et al. 2016

International Immunopharmacology

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Creatine is widely used by both elite and recreational athletes as an ergogenic aid to enhance anaerobic exercise performance. Older individuals also use creatine to prevent sarcopenia and, accordingly, may have therapeutic benefits for muscle wasting diseases. Although the effect of creatine on the musculoskeletal system has been extensively studied, less attention has been paid to its potential effects on other physiological systems. Because there is a significant pool of creatine in the brain, the utility of creatine supplementation has been examined in vitro as well as in vivo in both animal models of neurological disorders and in humans. While the data are preliminary, there is evidence to suggest that individuals with certain neurological conditions may benefit from exogenous creatine supplementation if treatment protocols can be optimized. A small number of studies that have examined the impact of creatine on the immune system have shown an alteration in soluble mediator production and the expression of molecules involved in recognizing infections, specifically toll-like receptors. Future investigations evaluating the total impact of creatine supplementation are required to better understand the benefits and risks of creatine use, particularly since there is increasing evidence that creatine may have a regulatory impact on the immune system.

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Nystatin Induces Secretion of Interleukin (IL)-1β, IL-8, and Tumor Necrosis Factor Alpha by a Toll-Like Receptor-Dependent Mechanism

Cited by 31 publications

References 17 publications

The Polymorphism P315L of Human Toll-Like Receptor 1 Impairs Innate Immune Sensing of Microbial Cell Wall Components

The Polymorphism P315L of Human Toll-Like Receptor 1 Impairs Innate Immune Sensing of Microbial Cell Wall Components

Polyene Macrolide Antifungal Drugs Trigger Interleukin-1β Secretion by Activating the NLRP3 Inflammasome

Beyond muscles: The untapped potential of creatine

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