Treatment with the Hyaluronic Acid Synthesis Inhibitor  4-Methylumbelliferone Suppresses SEB-Induced  Lung Inflammation

McKallip, Robert J.; H, Hägele; Uchakina, Olga N.

doi:10.3390/toxins5101814

Cited by 27 publications

(28 citation statements)

References 25 publications

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“…4-MU suppresses staphylococcal enterotoxin B- [279] and LPS-induced lung inflammation [280]. 4-MU treatment in vivo protected against central nervous system autoimmunity and increased CXCL12 expression in the inflamed nervous system [281].…”

Section: Ha As Therapeuticmentioning

confidence: 99%

Hyaluronan as a therapeutic target in human diseases

Liang

Jiang

Noble

2016

Advanced Drug Delivery Reviews

187

117

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Accumulation and turnover of extracellular matrix is a hallmark of tissue injury, repair and remodeling in human diseases. Hyaluronan is a major component of the extracellular matrix and plays an important role in regulating tissue injury and repair, and controlling disease outcomes. The function of hyaluronan depends on its size, location, and interactions with binding partners. While fragmented hyaluronan stimulates the expression of an array of genes by a variety of cell types regulating inflammatory responses and tissue repair, cell surface hyaluronan provides protection against tissue damage from the environment and promotes regeneration and repair. The interactions of hyaluronan and its binding proteins participate in the pathogenesis of many human diseases. Thus, targeting hyaluronan and its interactions with cells and proteins may provide new approaches to developing therapeutics for inflammatory and fibrosing diseases. This review focuses on the role of hyaluronan in biological and pathological processes, and as a potential therapeutic target in human diseases.

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Section: Ha As Therapeuticmentioning

confidence: 99%

Hyaluronan as a therapeutic target in human diseases

Liang

Jiang

Noble

2016

Advanced Drug Delivery Reviews

187

117

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“…Significantly increased HA production (by 32-fold in the circulation) has been found as a characteristic of patients with acute peripheral lung injury (20) and block HA production by hyaluronan synthase inhibitors effectively suppressed staphylococcal enterotoxin-induced inflammation (21). …”

Section: Introductionmentioning

confidence: 99%

Divergent Temporal Expression of Hyaluronan Metabolizing Enzymes and Receptors with Craniotomy vs. Controlled-Cortical Impact Injury in Rat Brain: A Pilot Study

2014

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Traumatic brain injury (TBI) triggers many secondary changes in tissue biology, which ultimately determine the extent of injury and clinical outcome. Hyaluronan [hyaluronic acid (HA)] is a protective cementing gel present in the intercellular spaces whose degradation has been reported as a causative factor in tissue damage. Yet little is known about the expression and activities of genes involved in HA catabolism after TBI. Young adult male Sprague-Dawley rats were assigned to three groups: naïve control, craniotomy, and controlled-cortical impact-induced TBI (CCI-TBI). Four animals per group were sacrificed at 4 h, 1, 3, and 7 days post-CCI. The mRNA expression of hyaluronan synthases (HAS1-3), hyaluronidases (enzymes for HA degradation, HYAL 1–4, and PH20), and CD44 and RHAMM (membrane receptors for HA signaling and removal) were determined using real-time PCR. Compared to the naïve controls, expression of HAS1 and HAS2 mRNA, but not HAS3 mRNA increased significantly following craniotomy alone and following CCI with differential kinetics. Expression of HAS2 mRNA increased significantly in the ipsilateral brain at 1 and 3 days post-CCI. HYAL1 mRNA expression also increased significantly in the craniotomy group and in the contralateral CCI at 1 and 3 days post-CCI. CD44 mRNA expression increased significantly in the ipsilateral CCI at 4 h, 1, 3, and 7 days post-CCI (up to 25-fold increase). These data suggest a dynamic regulation and role for HA metabolism in secondary responses to TBI.

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“…Three different approaches using "novel inhibitor" [4], an FDA-approved drug [5], or intravenous immunoglobulin (IVIG) therapy [6] are presented, addressing the urgent need for developing therapeutics against staphylococcal superantigens.…”

mentioning

confidence: 99%

“…The article "Treatment with the hyaluronic acid synthesis inhibitor 4-methylumbelliferone suppresses SEB-induced lung inflammation" presents the use of 4-methylumbelliferone (4-MU), an inhibitor of hyaluronic acid (HA) synthesis, to diminish SEB-induced lung inflammation in vivo [4]. In vitro studies using mouse splenocytes showed 4-MU inhibits SEB-induced T cell apoptosis and downregulates cytokine expression.…”

mentioning

confidence: 99%

Enterotoxins: Microbial Proteins and Host Cell Dysregulation

2016

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The special issue "Enterotoxins: Microbial Proteins and Host Cell Dysregulation" is comprised of research articles and reviews covering a diverse group of toxins that affect the gut and dysregulate host immune response in mechanistically different ways. Excellent in-depth reviews of staphylococcal superantigens and Clostridium perfringens toxins are the cornerstones of this issue. The present editorial highlights these papers grouped by toxin class and within each toxin class papers are discussed in order of publication date, with reviews appearing first, followed by original articles.The review entitled "Update on staphylococcal superantigen-induced signaling pathways and therapeutic interventions" gives a comprehensive review of signaling pathways induced by staphylococcal superantigens and evaluations of therapeutics targeting these pathways [1]. Of great interest is the presentation of pathways engaged by these bacterial superantigens, an extensive list of effective and ineffective therapies, as well as the benefits associated with specific targeting of activated molecules and pathways. A detailed pathway diagram of signaling molecules and points of intervention by specific inhibitors is available to readers.Another information-rich review, "Soluble T cell receptor Vβ domains engineered for high-affinity binding to staphylococcal or streptococcal superantigens", presents a brief review of the structure and sequence homology of multiple superantigens produced by Staphylococcus aureus and group A Streptococcus [2]. The different modes of binding of these superantigens to both major histocompatibility complex (MHC) class II and variable regions of T cell receptor beta chain (TCR Vβ) are presented, including the targeting of specific epitopes on superantigens with high affinity TCR Vβ mutants. A flow chart and schematic of yeast display methodology illustrate techniques used in the engineering of these soluble high affinity TCR Vβ domains against superantigens. The interaction of each specific high affinity Vβ domain against the superantigens SEA, SEB, SEC3, TSST-1, SpeA, and SpeC is displayed by their co-crystal structures. Of great interest to the scientific community is the utility of these high affinity TCR Vβ domains in blocking superantigen-induced lethality and preventing necrotizing pneumonia induced by SEC secreting methicillin-resistant S. aureus in various rabbit models of disease.The review article "Staphylococcal enterotoxins in the etiopathogenesis of mucosal autoimmunity within the gastrointestinal tract" addresses the immunopathogenic effects of staphylococcal enterotoxins in the gastrointestinal tract [3]. Different immune cell types, Th1, Th2, Th17 and regulatory T cells, participating in gut immune defense and tolerance are described. The early activation of specific Vβ T cells in blood and lymphoid organs results in induction of proinflammatory mediators (IL-1β, IL-2, IL-6, IL-8, MCP-1, IFNγ and TNFα) eliciting inflammatory cell infiltration to the gastrointestinal tract and the proliferation...

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Treatment with the Hyaluronic Acid Synthesis Inhibitor 4-Methylumbelliferone Suppresses SEB-Induced Lung Inflammation

Cited by 27 publications

References 25 publications

Hyaluronan as a therapeutic target in human diseases

Hyaluronan as a therapeutic target in human diseases

Divergent Temporal Expression of Hyaluronan Metabolizing Enzymes and Receptors with Craniotomy vs. Controlled-Cortical Impact Injury in Rat Brain: A Pilot Study

Enterotoxins: Microbial Proteins and Host Cell Dysregulation

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