Sphingosine-1-phosphate synthesis and functions in mast cells

Price, Megan M.; Oskeritzian, Carole A.; Milstien, Sheldon; Spiegel, Sarah

doi:10.2217/17460875.3.6.665

Cited by 16 publications

(18 citation statements)

References 75 publications

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“…In addition to cell migration, S1P and SphK1 are important for regulating immune cell functions. Activation of SphK1 is required for functional changes in mast cells following IgE cross-linking during allergic inflammatory responses including degranulation, NFkB activation, and the release of cytokines and chemokines [52][53][54]. In macrophages, both S1P and SphK1 are vital factors in regulating functional changes such as macrophage cell death Figure 2.…”

Section: Sphingosine Kinase 1 In Immune Cell Functionmentioning

confidence: 99%

Sphingosine kinase 1 in viral infections

Carr

Mahalingam

Bonder

et al. 2012

Reviews in Medical Virology

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Sphingosine kinase 1 (SphK1) is an enzyme that phosphorylates the lipid sphingosine to generate sphingosine-1-phosphate (S1P). S1P can act intracellularly as a signaling molecule and extracellularly as a receptor ligand. The SphK1/S1P axis has well-described roles in cell signaling, the cell death/survival decision, the production of a pro-inflammatory response, immunomodulation, and control of vascular integrity. Agents targeting the SphK1/S1P axis are being actively developed as therapeutics for cancer and immunological and inflammatory disorders. Control of cell death/survival and pro-inflammatory immune responses is central to the pathology of infectious disease, and we can capitalize on the knowledge provided by investigations of SphK1/S1P in cancer and immunology to assess its application to selected human infections. We have herein reviewed the growing literature relating viral infections to changes in SphK1 and S1P. SphK1 activity is reportedly increased following human cytomegalovirus and respiratory syncytial virus infections, and elevated SphK1 enhances influenza virus infection. In contrast, SphK1 activity is reduced in bovine viral diarrhea virus and dengue virus infections. Sphingosine analogs that modulate S1P receptors have proven useful in animal models in alleviating influenza virus infection but have shown no benefit in simian human immunodeficiency virus and lymphocytic choriomeningitis virus infections. We have rationalized a role for SphK1/S1P in dengue virus, chikungunya virus, and Ross River virus infections, on the basis of the biology and the pathology of these diseases. The increasing number of effective SphK1 and S1P modulating agents currently in development makes it timely to investigate these roles with the potential for developing modulators of SphK1 and S1P for novel anti-viral therapies.

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Section: Sphingosine Kinase 1 In Immune Cell Functionmentioning

confidence: 99%

Sphingosine kinase 1 in viral infections

Carr

Mahalingam

Bonder

et al. 2012

Reviews in Medical Virology

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“…Activation of S1P 1 is critical for migration of mast cells toward antigens and might be involved in the movement of mast cells up an antigen gradient to sites of inflammation. 22) Furthermore, expression of the motility-inhibiting S1P 2 receptor in mast cells is upregulated by antigen-mediated crosslinking of FcεRI, suggesting that mast cells accumulate at inflammation sites via an S1P 1 -dependent motility process and halt upon reaching their destination owing to upregulation of S1P 2 .…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Approach to Steroid-Resistant Dermatitis Using Novel Immunomodulator FTY720 (Fingolimod) in Combination with Betamethasone Ointment in NC/Nga Mice

Tsuji

Yoshida

Iwatsuki

et al. 2012

Biological & Pharmaceutical Bulletin

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The therapeutic efficacy of the novel immunomodulator FTY720 (Fingolimod), alone and in combination with betamethasone ointment, was examined in the NC/Nga mouse model of spontaneous steroid-resistant dermatitis. Male NC/Nga mice which had developed severe dermatitis were divided into six groups: 1) a biweekly betamethasone group (betamethasone ointment, twice a week), 2) a daily betamethasone group (betamethasone ointment, six times a week), 3) an FTY720 group (FTY720, orally, three times a week), 4) a biweekly combination group (oral FTY720 plus betamethasone ointment, twice a week), 5) a daily combination group (oral FTY720 plus betamethasone ointment, six times a week) and 6) a placebo group (vehicle alone). The therapeutic efficacy was evaluated in terms of severity of dermatitis, epidermal hypertrophy, accumulation and degranulation of mast cells and infiltrated CD3 T cells into the dermis after 4 weeks of treatment. Biweekly and daily betamethasone treatments had little effect, confirming that the dermatitis was steroidresistant. In the FTY720 and biweekly combination groups, the dermatitis showed no marked improvement. In the daily combination group, the dermatitis was significantly (p<0.05, Mann-Whitney U-test) improved as compared with the FTY720 group, biweekly and daily betamethasone groups and placebo group. Further, epidermal hypertrophy and accumulation of mast cells were suppressed. Therefore, combination therapy with FTY720 and daily betamethasone ointment is a promising candidate for treatment of steroid-resistant atopic dermatitis. Key words FTY720; NC/Nga mouse; atopic dermatitisThe novel immunomodulator FTY720 (Fingolimod) is a synthetic structural analogue of myriocin (ISP-I), a metabolite of Isaria cinclarii.

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“…Recently, many studies have suggested that sphingolipids, especially sphingosine 1-phosphate, are involved in the pathophysiology of mast cells (Price et al, 2008;Ryu et al, 2009). We speculated that lipid byproducts from abnormal skin barrier disruption, such as SPC, might induce the symptoms of atopic dermatitis.…”

Section: Inflammatory Lipidsmentioning

confidence: 97%

Progress of Pruritus Research in Atopic Dermatitis

Lee¹

2010

Biomolecules and Therapeutics

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-Atopic dermatitis is a common skin disease affecting up to 10% of children and approximately 2% of adults. Atopic dermatitis exhibits four major symptoms, including intense itching, dry skin, redness and exudation. The "itch-scratch-itch" cycle is one of the major features in atopic dermatitis. The pathophysiology and neurobiology of pruritus is unclear. Currently there are no single and universally effective pharmacological antipruritic drugs for treatment of atopic dermatitis. Thus, controlling of itch is a very important unmet need in patients suffering from atopic dermatitis. This article will update progress during the past 10 years of research in the field of pruritus of atopic dermatitis, focusing on aspects of pruritogens (including inflammatory lipids, histamine, serotonin, proteinases, proteinase-activating receptors, neurotransmitters, neuropeptides, and opioid peptides), antipruritic therapies, and emerging new targets. Based on recent progress, researchers expect to identify exciting possibilities for improved treatments and to develop new antipruritic drugs acting through novel targets, such as histamine H4 receptor, gastrin-releasing peptide receptor, MrgprA3, thromboxane A2 receptor and the putative SPC receptor. Keywords: Pruritus, Atopic dermatitis, Pruritogen, Antipruritic therapy, New targetAtopic dermatitis (AD) is a common skin disease that affects up to 10% of children and approximately 2% of adults in the general population (Leung and Soter, 2001). The socio-economic losses resulting from the disease are high; the cost of illness to the third-party payer for AD ranges from US $0.9 billion to US $3.8 billion (Ellis et al., 2002). The quality-of-life is remarkably lowered by AD. The genetic background, in combination with several environmental factors, results in this chronic remittent skin disease. AD exhibits four major symptoms including intense itching (pruritus), dry skin (xerosis), redness (erythema) and exudation. The "itch-scratch-itch" cycle is a common feature of AD. Scratching can cause bleeding, secondary infection (bacterial, fungal and/or viral) and thickening of the skin (lichenification) (Lewis-Jones, 2005). Itching is the predominant symptom of AD and is also an important diagnostic feature of systemic disease (Malekzad et al., 2009).The pathophysiology and neurobiology of pruritus are unclear. Therefore it is not surprising that anti-pruritus therapy is not well established and the choice of therapeutic agents is limited. However, recent progress over the past 10 years has provided insights into the neurophysiology of pruritus and is opening up exciting possibilities for development of new antipruritic drugs (Yosipovitch and Papoiu, 2008;Liu et al., 2009;Sun et al., 2009).Itch can be regarded as a cutaneous sensory perception, which requests excitation of specialized itch receptors in the skin. Increased amounts of neurofilament-, protein gene product (PGP) 9.5-, calcitonin gene-related peptide (CGRP)-, and substance P (SP)-positive nerve fibres have been observe...

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Sphingosine-1-phosphate synthesis and functions in mast cells

Cited by 16 publications

References 75 publications

Sphingosine kinase 1 in viral infections

Sphingosine kinase 1 in viral infections

Therapeutic Approach to Steroid-Resistant Dermatitis Using Novel Immunomodulator FTY720 (Fingolimod) in Combination with Betamethasone Ointment in NC/Nga Mice

Progress of Pruritus Research in Atopic Dermatitis

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