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  1. Article ; Online: We need to talk about lung cancer's cholesterol-hoarding problem.

    Fessler, Michael B

    Cell stem cell

    2023  Volume 30, Issue 6, Page(s) 745–747

    Abstract: Proliferative cells require excess cholesterol to support rapid membrane biogenesis. Using a mutant KRAS mouse model of non-small cell lung cancer, Guilbaud et al. show that lung cancers accumulate cholesterol by locally and distally reprogramming lipid ... ...

    Abstract Proliferative cells require excess cholesterol to support rapid membrane biogenesis. Using a mutant KRAS mouse model of non-small cell lung cancer, Guilbaud et al. show that lung cancers accumulate cholesterol by locally and distally reprogramming lipid trafficking and that cholesterol-removing interventions may hold promise as a therapeutic strategy.
    MeSH term(s) Animals ; Mice ; Carcinoma, Non-Small-Cell Lung/drug therapy ; Lung Neoplasms/drug therapy ; Hoarding ; Disease Models, Animal ; Cholesterol
    Chemical Substances Cholesterol (97C5T2UQ7J)
    Language English
    Publishing date 2023-05-25
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Intramural
    ZDB-ID 2375354-7
    ISSN 1875-9777 ; 1934-5909
    ISSN (online) 1875-9777
    ISSN 1934-5909
    DOI 10.1016/j.stem.2023.05.006
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 6589: Show issues Location:
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  2. Article: Oxysterols in Infectious Diseases.

    Foo, Cheng X / Fessler, Michael B / Ronacher, Katharina

    Advances in experimental medicine and biology

    2023  Volume 1440, Page(s) 125–147

    Abstract: Oxysterols have emerged as important bioactive lipids in the immune response to infectious diseases. This chapter discusses our current knowledge of oxysterols and their receptors in bacterial and viral infections of the respiratory and gastrointestinal ... ...

    Abstract Oxysterols have emerged as important bioactive lipids in the immune response to infectious diseases. This chapter discusses our current knowledge of oxysterols and their receptors in bacterial and viral infections of the respiratory and gastrointestinal tracts. Oxysterols are produced in response to infections and have multiple roles including chemotaxis of immune cells to the site of infection and regulation of inflammation. Some oxysterols have been shown to possess antiviral or antibacterial activity.Lastly, we delve into the emerging mechanisms of action of oxysterols. Oxysterols can enhance host cell resistance via reduction of membrane accessible cholesterol, modulate membrane immune signalling, and impact inflammasome activation and efferocytosis.
    MeSH term(s) Humans ; Oxysterols/metabolism ; Cholesterol/metabolism ; Inflammation ; Signal Transduction ; Communicable Diseases
    Chemical Substances Oxysterols ; Cholesterol (97C5T2UQ7J)
    Language English
    Publishing date 2023-12-01
    Publishing country United States
    Document type Journal Article
    ZDB-ID 410187-X
    ISSN 0065-2598
    ISSN 0065-2598
    DOI 10.1007/978-3-031-43883-7_7
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Einzelsignatur: Show issues

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  3. Article ; Online: Drugging the Mighty Neutrophil in Chronic Obstructive Pulmonary Disease.

    Fessler, Michael B

    American journal of respiratory cell and molecular biology

    2018  Volume 60, Issue 4, Page(s) 382–383

    MeSH term(s) Aminopyridines ; Benzamides ; Cyclopropanes ; Humans ; Neutrophils ; Phosphodiesterase 4 Inhibitors ; Pulmonary Disease, Chronic Obstructive
    Chemical Substances Aminopyridines ; Benzamides ; Cyclopropanes ; Phosphodiesterase 4 Inhibitors ; Roflumilast (0P6C6ZOP5U)
    Language English
    Publishing date 2018-12-03
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 1025960-0
    ISSN 1535-4989 ; 1044-1549
    ISSN (online) 1535-4989
    ISSN 1044-1549
    DOI 10.1165/rcmb.2018-0370ED
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    Zs.A 2851: Show issues Location:
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  4. Article ; Online: The MAVS and MAV-Nots: PINK1 Clears Prion-like MAVS Aggregates to Extinguish Mitochondrial Inflammatory Signaling.

    Rai, Prashant / Fessler, Michael B

    American journal of respiratory cell and molecular biology

    2021  Volume 64, Issue 5, Page(s) 528–530

    MeSH term(s) Adaptor Proteins, Signal Transducing/metabolism ; Prions ; Protein Kinases ; Signal Transduction
    Chemical Substances Adaptor Proteins, Signal Transducing ; Prions ; Protein Kinases (EC 2.7.-)
    Language English
    Publishing date 2021-03-10
    Publishing country United States
    Document type Editorial ; Research Support, N.I.H., Intramural ; Comment
    ZDB-ID 1025960-0
    ISSN 1535-4989 ; 1044-1549
    ISSN (online) 1535-4989
    ISSN 1044-1549
    DOI 10.1165/rcmb.2021-0055ED
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  5. Article ; Online: Regulatory mechanisms of neutrophil migration from the circulation to the airspace.

    Lin, Wan-Chi / Fessler, Michael B

    Cellular and molecular life sciences : CMLS

    2021  Volume 78, Issue 9, Page(s) 4095–4124

    Abstract: The neutrophil, a short-lived effector leukocyte of the innate immune system best known for its proteases and other degradative cargo, has unique, reciprocal physiological interactions with the lung. During health, large numbers of 'marginated' ... ...

    Abstract The neutrophil, a short-lived effector leukocyte of the innate immune system best known for its proteases and other degradative cargo, has unique, reciprocal physiological interactions with the lung. During health, large numbers of 'marginated' neutrophils reside within the pulmonary vasculature, where they patrol the endothelial surface for pathogens and complete their life cycle. Upon respiratory infection, rapid and sustained recruitment of neutrophils through the endothelial barrier, across the extravascular pulmonary interstitium, and again through the respiratory epithelium into the airspace lumen, is required for pathogen killing. Overexuberant neutrophil trafficking to the lung, however, causes bystander tissue injury and underlies several acute and chronic lung diseases. Due in part to the unique architecture of the lung's capillary network, the neutrophil follows a microanatomic passage into the distal airspace unlike that observed in other end-organs that it infiltrates. Several of the regulatory mechanisms underlying the stepwise recruitment of circulating neutrophils to the infected lung have been defined over the past few decades; however, fundamental questions remain. In this article, we provide an updated review and perspective on emerging roles for the neutrophil in lung biology, on the molecular mechanisms that control the trafficking of neutrophils to the lung, and on past and ongoing efforts to design therapeutics to intervene upon pulmonary neutrophilia in lung disease.
    MeSH term(s) Chemokines/metabolism ; Chemotactic Factors/pharmacology ; Cytokines/metabolism ; Endothelium/immunology ; Endothelium/metabolism ; Extracellular Matrix/metabolism ; Humans ; Lung/immunology ; Lung/metabolism ; Lung Diseases/immunology ; Lung Diseases/metabolism ; Lung Diseases/pathology ; Neutrophil Infiltration/drug effects ; Neutrophil Infiltration/physiology ; Neutrophils/cytology ; Neutrophils/immunology ; Neutrophils/metabolism
    Chemical Substances Chemokines ; Chemotactic Factors ; Cytokines
    Language English
    Publishing date 2021-02-05
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 1358415-7
    ISSN 1420-9071 ; 1420-682X
    ISSN (online) 1420-9071
    ISSN 1420-682X
    DOI 10.1007/s00018-021-03768-z
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 195: Show issues Location:
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  6. Article ; Online: CO

    Fessler, Michael B

    American journal of respiratory cell and molecular biology

    2017  Volume 57, Issue 5, Page(s) 499–500

    MeSH term(s) Adipocytes/metabolism ; Adipocytes/pathology ; Adipogenesis ; Adipose Tissue, White/metabolism ; Adipose Tissue, White/pathology ; Animals ; Carbon Dioxide/metabolism ; Humans ; Obesity/metabolism ; Obesity/pathology ; PPAR gamma/metabolism
    Chemical Substances PPAR gamma ; Carbon Dioxide (142M471B3J)
    Language English
    Publishing date 2017-11-01
    Publishing country United States
    Document type Editorial ; Research Support, N.I.H., Intramural
    ZDB-ID 1025960-0
    ISSN 1535-4989 ; 1044-1549
    ISSN (online) 1535-4989
    ISSN 1044-1549
    DOI 10.1165/rcmb.2017-0222ED
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  7. Article ; Online: A New Frontier in Immunometabolism. Cholesterol in Lung Health and Disease.

    Fessler, Michael B

    Annals of the American Thoracic Society

    2017  Volume 14, Issue Supplement_5, Page(s) S399–S405

    Abstract: The lung has a unique relationship to cholesterol that is shaped by its singular physiology. On the one hand, the lungs receive the full cardiac output and have a predominant dependence on plasma lipoprotein uptake for their cholesterol supply. On the ... ...

    Abstract The lung has a unique relationship to cholesterol that is shaped by its singular physiology. On the one hand, the lungs receive the full cardiac output and have a predominant dependence on plasma lipoprotein uptake for their cholesterol supply. On the other hand, surfactant lipids, including cholesterol, are continually susceptible to oxidation owing to direct environmental exposure and must be cleared or recycled because of the very narrow biophysical mandates placed upon surfactant lipid composition. Interestingly, increased lipid-laden macrophage "foam cells" have been noted in a wide range of human lung pathologies. This suggests that lipid dysregulation may be a unifying and perhaps contributory event in chronic lung disease pathogenesis. Recent studies have shown that perturbations in intracellular cholesterol trafficking critically modify the immune response of macrophages and other cells. This minireview discusses literature that has begun to demonstrate the importance of regulated cholesterol traffic through the lung to pulmonary immunity, inflammation, and fibrosis. This emerging recognition of coupling between immunity and lipid homeostasis in the lung presents potentially transformative concepts for understanding lung disease and may also offer novel and exciting avenues for therapeutic development.
    MeSH term(s) ATP-Binding Cassette Transporters/metabolism ; Adaptive Immunity ; Animals ; Cholesterol/metabolism ; Homeostasis ; Humans ; Immunity, Innate ; Lipoproteins/blood ; Lung/immunology ; Lung Diseases/physiopathology ; Macrophages/immunology ; Mice
    Chemical Substances ATP-Binding Cassette Transporters ; Lipoproteins ; Cholesterol (97C5T2UQ7J)
    Language English
    Publishing date 2017-11-21
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2717461-X
    ISSN 2325-6621 ; 1943-5665 ; 2325-6621
    ISSN (online) 2325-6621 ; 1943-5665
    ISSN 2325-6621
    DOI 10.1513/AnnalsATS.201702-136AW
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 5828: Show issues Location:
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  8. Article ; Online: The challenges and promise of targeting the Liver X Receptors for treatment of inflammatory disease.

    Fessler, Michael B

    Pharmacology & therapeutics

    2017  Volume 181, Page(s) 1–12

    Abstract: The Liver X Receptors (LXRs) are oxysterol-activated transcription factors that upregulate a suite of genes that together promote coordinated mobilization of excess cholesterol from cells and from the body. The LXRs, like other nuclear receptors, are ... ...

    Abstract The Liver X Receptors (LXRs) are oxysterol-activated transcription factors that upregulate a suite of genes that together promote coordinated mobilization of excess cholesterol from cells and from the body. The LXRs, like other nuclear receptors, are anti-inflammatory, inhibiting signal-dependent induction of pro-inflammatory genes by nuclear factor-κB, activating protein-1, and other transcription factors. Synthetic LXR agonists have been shown to ameliorate atherosclerosis and a wide range of inflammatory disorders in preclinical animal models. Although this has suggested potential for application to human disease, systemic LXR activation is complicated by hepatic steatosis and hypertriglyceridemia, consequences of lipogenic gene induction in the liver by LXRα. The past several years have seen the development of multiple advanced LXR therapeutics aiming to avoid hepatic lipogenesis, including LXRβ-selective agonists, tissue-selective agonists, and transrepression-selective agonists. Although several synthetic LXR agonists have made it to phase I clinical trials, none have progressed due to unforeseen adverse reactions or undisclosed reasons. Nonetheless, several sophisticated pharmacologic strategies, including structure-guided drug design, cell-specific drug targeting, as well as non-systemic drug routes have been initiated and remain to be comprehensively explored. In addition, recent studies have identified potential utility for targeting the LXRs during therapy with other agents, such as glucocorticoids and rexinoids. Despite the pitfalls encountered to date in translation of LXR agonists to human disease, it appears likely that this accelerating field will ultimately yield effective and safe applications for LXR targeting in humans.
    MeSH term(s) Animals ; Atherosclerosis/drug therapy ; Benzoates/pharmacology ; Benzoates/therapeutic use ; Benzylamines/pharmacology ; Benzylamines/therapeutic use ; Gene Expression Regulation/drug effects ; Humans ; Hydrocarbons, Fluorinated/pharmacology ; Hydrocarbons, Fluorinated/therapeutic use ; Inflammation/drug therapy ; Liver X Receptors/agonists ; Liver X Receptors/physiology ; Models, Biological ; Molecular Targeted Therapy/methods ; Sulfonamides/pharmacology ; Sulfonamides/therapeutic use
    Chemical Substances Benzoates ; Benzylamines ; GW 3965 ; Hydrocarbons, Fluorinated ; Liver X Receptors ; Sulfonamides ; T0901317
    Language English
    Publishing date 2017-07-16
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Intramural ; Review
    ZDB-ID 194735-7
    ISSN 1879-016X ; 0163-7258
    ISSN (online) 1879-016X
    ISSN 0163-7258
    DOI 10.1016/j.pharmthera.2017.07.010
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  9. Article ; Online: Running interference on miR-33: a new amplification loop for type I interferon in the host antiviral response.

    Zhao, Fei / Fessler, Michael B

    Cellular & molecular immunology

    2020  Volume 17, Issue 10, Page(s) 1109–1110

    MeSH term(s) Adaptor Proteins, Signal Transducing/metabolism ; Animals ; Antiviral Agents/metabolism ; Host-Pathogen Interactions/genetics ; Humans ; Interferon Type I/metabolism ; MicroRNAs/genetics ; MicroRNAs/metabolism
    Chemical Substances Adaptor Proteins, Signal Transducing ; Antiviral Agents ; Interferon Type I ; MicroRNAs
    Keywords covid19
    Language English
    Publishing date 2020-02-13
    Publishing country China
    Document type Letter ; Research Support, N.I.H., Intramural
    ZDB-ID 2435097-7
    ISSN 2042-0226 ; 1672-7681
    ISSN (online) 2042-0226
    ISSN 1672-7681
    DOI 10.1038/s41423-020-0373-3
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  10. Article ; Online: The Intracellular Cholesterol Landscape: Dynamic Integrator of the Immune Response.

    Fessler, Michael B

    Trends in immunology

    2016  Volume 37, Issue 12, Page(s) 819–830

    Abstract: Cholesterol has typically been considered an exogenous, disease-related factor in immunity; however, recent literature suggests that a paradigm shift is in order. Sterols are now recognized to ligate several immune receptors. Altered flux through the ... ...

    Abstract Cholesterol has typically been considered an exogenous, disease-related factor in immunity; however, recent literature suggests that a paradigm shift is in order. Sterols are now recognized to ligate several immune receptors. Altered flux through the mevalonic acid synthesis pathway also appears to be a required event in the antiviral interferon (IFN) response of macrophages and in the activation, proliferation, and differentiation of T cells. In this review, evidence is discussed that suggests an intrinsic, 'professional' role for sterols and oxysterols in macrophage and T-cell immunity. Host defense may have been the original selection pressure behind the development of mechanisms for intracellular cholesterol homeostasis. Functional coupling between sterol metabolism and immunity has fundamental implications for health and disease.
    MeSH term(s) Animals ; Cholesterol/metabolism ; Homeostasis ; Humans ; Immunity ; Interferons/immunology ; Intracellular Space/metabolism ; Macrophages/immunology ; Mevalonic Acid/metabolism ; Receptors, Immunologic/metabolism ; Signal Transduction ; T-Lymphocytes/immunology
    Chemical Substances Receptors, Immunologic ; Interferons (9008-11-1) ; Cholesterol (97C5T2UQ7J) ; Mevalonic Acid (S5UOB36OCZ)
    Language English
    Publishing date 2016-09-28
    Publishing country England
    Document type Journal Article ; Review ; Research Support, N.I.H., Intramural
    ZDB-ID 2036831-8
    ISSN 1471-4981 ; 1471-4906
    ISSN (online) 1471-4981
    ISSN 1471-4906
    DOI 10.1016/j.it.2016.09.001
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.MG 2: Show issues

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