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Interleukin 4 induces rapid mucin transport, increases mucus thickness and quality and decreases colitis and Citrobacter rodentium in contact with epithelial cells

Artikel i vetenskaplig tidskrift
Författare Sinan Sharba
Nazanin Navabi
Médea Padra
Macarena P Quintana-Hayashi
Jenny K Gustafsson
Louis Szeponik
Vignes Venkatakrishnan
A. Sjoling
Staffan Nilsson
Marianne Quiding-Järbrink
Malin E V Johansson
Sara K. Lindén
Publicerad i Virulence
Volym 10
Nummer/häfte 1
Sidor 97-117
ISSN 2150-5594
Publiceringsår 2019
Publicerad vid Institutionen för biomedicin, avdelningen för patologi
Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi
Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi
Sidor 97-117
Språk en
Länkar dx.doi.org/10.1080/21505594.2019.15...
Ämnesord Mucin, mucus, mucosa, Citrobacter rodentium, A/E pathogen, cytokine, IL-4, IFN-gamma, colitis, gene-expression, infection impairs, n-acetylcysteine, messenger-rna, mouse small, tnf-alpha, mice, secretion, line, differentiation, Immunology, Infectious Diseases, Microbiology, ates of america, v105, p15064
Ämneskategorier Immunologi

Sammanfattning

Citrobacter rodentium infection is a murine model for pathogenic intestinal Escherichia coli infection. C. rodentium infection causes an initial decrease in mucus layer thickness, followed by an increase during clearance. We aimed to identify the cause of these changes and to utilize this naturally occurring mucus stimulus to decrease pathogen impact and inflammation. We identified that mucin production and speed of transport from Golgi to secretory vesicles at the apical surface increased concomitantly with increased mucus thickness. Of the cytokines differentially expressed during increased mucus thickness, IFN-gamma and TNF-alpha decreased the mucin production and transport speed, whereas IL-4, IL-13, C. rodentium and E. coli enhanced these aspects. IFN-gamma and TNF-alpha treatment in combination with C. rodentium and pathogenic E. coli infection negatively affected mucus parameters in vitro, which was relieved by IL-4 treatment. The effect of IL-4 was more pronounced than that of IL-13, and in wild type mice, only IL-4 was present. Increased expression of Il-4, Il-4-receptor alpha, Stat6 and Spdef during clearance indicate that this pathway contributes to the increase in mucin production. In vivo IL-4 administration initiated 10 days after infection increased mucus thickness and quality and decreased colitis and pathogen contact with the epithelium. Thus, during clearance of infection, the concomitant increase in IL-4 protects and maintains goblet cell function against the increasing levels of TNF-alpha and IFN-gamma. Furthermore, IL-4 affects intestinal mucus production, pathogen contact with the epithelium and colitis. IL-4 treatment may thus have therapeutic benefits for mucosal healing.

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Denna text är utskriven från följande webbsida:
http://www.gu.se/forskning/publikation/?publicationId=278141
Utskriftsdatum: 2019-08-19