Search our Database of Scientific Publications and Authors

I’m looking for a

    Details and Download Full Text PDF:
    PGE2 induced in and released by dying cells functions as an inhibitory DAMP.

    Proc Natl Acad Sci U S A 2016 Apr 21;113(14):3844-9. Epub 2016 Mar 21.
    Department of Molecular Immunology, Institute of Industrial Science, The University of Tokyo, Komaba 4-6-1, Meguro-ku, Tokyo 153-8505, Japan; Max Planck-The University of Tokyo Center for Integrative Inflammology, Komaba 4-6-1, Meguro-ku, Tokyo 153-8505, Japan;
    Cellular components released into the external milieu as a result of cell death and sensed by the body are generally termed damage-associated molecular patterns (DAMPs). Although DAMPs are conventionally thought to be protective to the host by evoking inflammatory responses important for immunity and wound repair, there is the prevailing notion that dysregulated release of DAMPs can also underlie or exacerbate disease development. However, the critical issue for how resultant DAMP-mediated responses are regulated has heretofore not been fully addressed. In the present study, we identify prostaglandin E2 (PGE2) as a DAMP that negatively regulates immune responses. We show that the production of PGE2 is augmented under cell death-inducing conditions via the transcriptional induction of the cyclooxygenase 2 (COX2) gene and that cell-released PGE2 suppresses the expression of genes associated with inflammation, thereby limiting the cell's immunostimulatory activities. Consistent with this, inhibition of the PGE2 synthesis pathway potentiates the inflammation induced by dying cells. We also provide in vivo evidence for a protective role of PGE2 released upon acetaminophen-induced liver injury as well as a pathogenic role for PGE2 during tumor cell growth. Our study places this classically known lipid mediator in an unprecedented context-that is, an inhibitory DAMP vis-à-vis activating DAMPs, which may have translational implications for designing more effective therapeutic regimens for inflammation-associated diseases.
    PDF Download - Full Text Link
    ( Please be advised that this article is hosted on an external website not affiliated with PubFacts.com)
    Source Status
    http://dx.doi.org/10.1073/pnas.1602023113DOI ListingPossible
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4833254PMCFound

    Similar Publications

    NMI and IFP35 serve as proinflammatory DAMPs during cellular infection and injury.
    Nat Commun 2017 10 16;8(1):950. Epub 2017 Oct 16.
    National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
    Damage-associated molecular patterns (DAMP) trigger innate immune response and exacerbate inflammation to combat infection and cellular damage. Identifying DAMPs and revealing their functions are thus of crucial importance. Here we report that two molecules, N-myc and STAT interactor (NMI) and interferon-induced protein 35 (IFP35) act as DAMPs and are released by activated macrophages during lipopolysaccharide-induced septic shock or acetaminophen-induced liver injury. Read More
    Damage-associated molecular patterns in cancer: a double-edged sword.
    Oncogene 2016 11 18;35(46):5931-5941. Epub 2016 Apr 18.
    Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
    Damage-associated molecular patterns (DAMPs) are released in response to cell death and stress, and are potent triggers of sterile inflammation. Recent evidence suggests that DAMPs may also have a key role in the development of cancer, as well as in the host response to cytotoxic anti-tumor therapy. As such, DAMPs may exert protective functions by alerting the immune system to the presence of dying tumor cells, thereby triggering immunogenic tumor cell death. Read More
    Susceptibility for cigarette smoke-induced DAMP release and DAMP-induced inflammation in COPD.
    Am J Physiol Lung Cell Mol Physiol 2016 11 9;311(5):L881-L892. Epub 2016 Sep 9.
    Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
    Cigarette smoke (CS) exposure is a major risk factor for chronic obstructive pulmonary disease (COPD). We investigated whether CS-induced damage-associated molecular pattern (DAMP) release or DAMP-mediated inflammation contributes to susceptibility for COPD. Samples, including bronchial brushings, were collected from young and old individuals, susceptible and nonsusceptible for the development of COPD, before and after smoking, and used for gene profiling and airway epithelial cell (AEC) culture. Read More
    Evaluation of the contribution of multiple DAMPs and DAMP receptors in cell death-induced sterile inflammatory responses.
    PLoS One 2014 15;9(8):e104741. Epub 2014 Aug 15.
    Department of Pathology, UMass Medical School, Worcester, Massachusetts, United States of America.
    When cells die by necrosis in vivo they stimulate an inflammatory response. It is thought that this response is triggered when the injured cells expose proinflammatory molecules, collectively referred to as damage associated molecular patterns (DAMPs), which are recognized by cells or soluble molecules of the innate or adaptive immune system. Several putative DAMPs and/or their receptors have been identified, but whether and how much they participate in responses in vivo is incompletely understood, and they have not previously been compared side-by-side in the same models. Read More