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Galectins regulate the inflammatory response in airway epithelial cells exposed to microbial neuraminidase by modulating the expression of SOCS1 and RIG1.
- Source :
-
Molecular immunology [Mol Immunol] 2015 Dec; Vol. 68 (2 Pt A), pp. 194-202. Date of Electronic Publication: 2015 Sep 06. - Publication Year :
- 2015
-
Abstract
- Influenza patients frequently display increased susceptibility to Streptococcus pneumoniae co-infection and sepsis, the prevalent cause of mortality during influenza pandemics. However, the detailed mechanisms by which an influenza infection predisposes patients to suffer pneumococcal pneumonia are not fully understood. A murine model for influenza infection closely reflects the observations in human patients, since if the animals that have recovered from influenza A virus (IAV) sublethal infection are challenged with S. pneumoniae, they undergo a usually fatal uncontrolled cytokine response. We have previously demonstrated both in vitro and in vivo that the expression and secretion of galectin-1 (Gal1) and galectin-3 (Gal3) are modulated during IAV infection, and that the viral neuraminidase unmasks galactosyl moieties in the airway epithelia. In this study we demonstrate in vitro that the binding of secreted Gal1 and Gal3 to the epithelial cell surface modulates the expression of SOCS1 and RIG1, and activation of ERK, AKT or JAK/STAT1 signaling pathways, leading to a disregulated expression and release of pro-inflammatory cytokines. Our results suggest that the activity of the viral and pneumococcal neuraminidases on the surface of the airway epithelial cells function as a "danger signal" that leads to rapid upregulation of SOCS1 expression to prevent an uncontrolled inflammatory response. The binding of extracellular Gal1 or Gal3 to the galactosyl moieties unmasked on the surface of airway epithelial cells can either "fine-tune" or severely disregulate this process, respectively, the latter potentially leading to hypercytokinemia.<br /> (Copyright © 2015 Elsevier Ltd. All rights reserved.)
- Subjects :
- Animals
Bacterial Proteins pharmacology
Cell Line, Tumor
Cytokines biosynthesis
Cytokines metabolism
DEAD Box Protein 58
DEAD-box RNA Helicases immunology
DEAD-box RNA Helicases pharmacology
Epithelial Cells cytology
Epithelial Cells drug effects
Escherichia coli genetics
Escherichia coli metabolism
Extracellular Signal-Regulated MAP Kinases genetics
Extracellular Signal-Regulated MAP Kinases immunology
Galectin 1 biosynthesis
Galectin 1 immunology
Galectin 3 biosynthesis
Galectin 3 immunology
Gene Expression Regulation
Humans
Inflammation
Influenza A virus immunology
Janus Kinases genetics
Janus Kinases immunology
Mice
Neuraminidase pharmacology
Proto-Oncogene Proteins c-akt genetics
Proto-Oncogene Proteins c-akt immunology
Receptors, Immunologic
Recombinant Proteins biosynthesis
Recombinant Proteins immunology
Recombinant Proteins pharmacology
Respiratory Mucosa cytology
Respiratory Mucosa drug effects
Respiratory Mucosa immunology
STAT1 Transcription Factor genetics
STAT1 Transcription Factor immunology
Signal Transduction
Suppressor of Cytokine Signaling 1 Protein
Suppressor of Cytokine Signaling Proteins immunology
Suppressor of Cytokine Signaling Proteins pharmacology
DEAD-box RNA Helicases genetics
Epithelial Cells immunology
Galectin 1 pharmacology
Galectin 3 pharmacology
Suppressor of Cytokine Signaling Proteins genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1872-9142
- Volume :
- 68
- Issue :
- 2 Pt A
- Database :
- MEDLINE
- Journal :
- Molecular immunology
- Publication Type :
- Academic Journal
- Accession number :
- 26355912
- Full Text :
- https://doi.org/10.1016/j.molimm.2015.08.005