Morphine Attenuates Apically-Directed Cytokine Secretion from Intestinal Epithelial Cells in Response to Enteric Pathogens

Epithelial cells represent the first line of host immune defense at mucosal surfaces. Although opioids appear to increase host susceptibility to infection, no studies have examined opioid effects on epithelial immune functions. We tested the hypothesis that morphine alters vectorial cytokine secreti...

Full description

Bibliographic Details
Main Authors: Amanda J. Brosnahan, Bryan J. Jones, Cheryl M. Dvorak, David R. Brown
Format: Article
Language:English
Published: MDPI AG 2014-04-01
Series:Pathogens
Subjects:
Online Access:http://www.mdpi.com/2076-0817/3/2/249
_version_ 1818007902653251584
author Amanda J. Brosnahan
Bryan J. Jones
Cheryl M. Dvorak
David R. Brown
author_facet Amanda J. Brosnahan
Bryan J. Jones
Cheryl M. Dvorak
David R. Brown
author_sort Amanda J. Brosnahan
collection DOAJ
description Epithelial cells represent the first line of host immune defense at mucosal surfaces. Although opioids appear to increase host susceptibility to infection, no studies have examined opioid effects on epithelial immune functions. We tested the hypothesis that morphine alters vectorial cytokine secretion from intestinal epithelial cell (IPEC-J2) monolayers in response to enteropathogens. Both entero-adherent Escherichia coli O157:H7 and entero-invasive Salmonella enterica serovar Typhimurium increased apically-directed IL-6 secretion and bi-directional IL-8 secretion from epithelial monolayers, but only IL-6 secretion evoked by E. coli was reduced by morphine acting through a naloxone-sensitive mechanism. Moreover, the respective type 4 and 5 Toll-like receptor agonists, lipopolysaccharide and flagellin, increased IL-8 secretion from monolayers, which was also attenuated by morphine pretreatment. These results suggest that morphine decreases cytokine secretion and potentially phagocyte migration and activation directed towards the mucosal surface; actions that could increase host susceptibility to some enteric infections.
first_indexed 2024-04-14T05:21:57Z
format Article
id doaj.art-c5bc94ad8bd24c4db4983736096e5af1
institution Directory Open Access Journal
issn 2076-0817
language English
last_indexed 2024-04-14T05:21:57Z
publishDate 2014-04-01
publisher MDPI AG
record_format Article
series Pathogens
spelling doaj.art-c5bc94ad8bd24c4db4983736096e5af12022-12-22T02:10:09ZengMDPI AGPathogens2076-08172014-04-013224925710.3390/pathogens3020249pathogens3020249Morphine Attenuates Apically-Directed Cytokine Secretion from Intestinal Epithelial Cells in Response to Enteric PathogensAmanda J. Brosnahan0Bryan J. Jones1Cheryl M. Dvorak2David R. Brown3Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, 1988 Fitch Avenue, Saint Paul, MN 55108-6010, USADepartment of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, 1988 Fitch Avenue, Saint Paul, MN 55108-6010, USADepartment of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, 1988 Fitch Avenue, Saint Paul, MN 55108-6010, USADepartment of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, 1988 Fitch Avenue, Saint Paul, MN 55108-6010, USAEpithelial cells represent the first line of host immune defense at mucosal surfaces. Although opioids appear to increase host susceptibility to infection, no studies have examined opioid effects on epithelial immune functions. We tested the hypothesis that morphine alters vectorial cytokine secretion from intestinal epithelial cell (IPEC-J2) monolayers in response to enteropathogens. Both entero-adherent Escherichia coli O157:H7 and entero-invasive Salmonella enterica serovar Typhimurium increased apically-directed IL-6 secretion and bi-directional IL-8 secretion from epithelial monolayers, but only IL-6 secretion evoked by E. coli was reduced by morphine acting through a naloxone-sensitive mechanism. Moreover, the respective type 4 and 5 Toll-like receptor agonists, lipopolysaccharide and flagellin, increased IL-8 secretion from monolayers, which was also attenuated by morphine pretreatment. These results suggest that morphine decreases cytokine secretion and potentially phagocyte migration and activation directed towards the mucosal surface; actions that could increase host susceptibility to some enteric infections.http://www.mdpi.com/2076-0817/3/2/249morphineopioid receptorssmall intestineepithelial cellEscherichia coliSalmonella entericainterleukin-6interleukin-8Toll-like receptorsswine
spellingShingle Amanda J. Brosnahan
Bryan J. Jones
Cheryl M. Dvorak
David R. Brown
Morphine Attenuates Apically-Directed Cytokine Secretion from Intestinal Epithelial Cells in Response to Enteric Pathogens
Pathogens
morphine
opioid receptors
small intestine
epithelial cell
Escherichia coli
Salmonella enterica
interleukin-6
interleukin-8
Toll-like receptors
swine
title Morphine Attenuates Apically-Directed Cytokine Secretion from Intestinal Epithelial Cells in Response to Enteric Pathogens
title_full Morphine Attenuates Apically-Directed Cytokine Secretion from Intestinal Epithelial Cells in Response to Enteric Pathogens
title_fullStr Morphine Attenuates Apically-Directed Cytokine Secretion from Intestinal Epithelial Cells in Response to Enteric Pathogens
title_full_unstemmed Morphine Attenuates Apically-Directed Cytokine Secretion from Intestinal Epithelial Cells in Response to Enteric Pathogens
title_short Morphine Attenuates Apically-Directed Cytokine Secretion from Intestinal Epithelial Cells in Response to Enteric Pathogens
title_sort morphine attenuates apically directed cytokine secretion from intestinal epithelial cells in response to enteric pathogens
topic morphine
opioid receptors
small intestine
epithelial cell
Escherichia coli
Salmonella enterica
interleukin-6
interleukin-8
Toll-like receptors
swine
url http://www.mdpi.com/2076-0817/3/2/249
work_keys_str_mv AT amandajbrosnahan morphineattenuatesapicallydirectedcytokinesecretionfromintestinalepithelialcellsinresponsetoentericpathogens
AT bryanjjones morphineattenuatesapicallydirectedcytokinesecretionfromintestinalepithelialcellsinresponsetoentericpathogens
AT cherylmdvorak morphineattenuatesapicallydirectedcytokinesecretionfromintestinalepithelialcellsinresponsetoentericpathogens
AT davidrbrown morphineattenuatesapicallydirectedcytokinesecretionfromintestinalepithelialcellsinresponsetoentericpathogens