Lung epithelial barrier function and wound healing are decreased by IL-4 and IL-13 and enhanced by IFN-gamma
Departments of Biomolecular Screening and Protein Chemistry, Immunex Corporation, Seattle, Washington 98101 To understand the effects of cytokines on epithelial cells in asthma, we have investigated the effects of interleukin (IL)-4, IL-13, and interferon (IFN)- on barrier function and wound healing...
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| Veröffentlicht in: | American Journal of Physiology: Cell Physiology 2001-12, Vol.281 (6), p.C2029-C2038 |
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| container_title | American Journal of Physiology: Cell Physiology |
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| creator | Ahdieh, Minoo Vandenbos, Tim Youakim, Adel |
| description | Departments of Biomolecular Screening and Protein Chemistry,
Immunex Corporation, Seattle, Washington 98101
To understand the
effects of cytokines on epithelial cells in asthma, we have
investigated the effects of interleukin (IL)-4, IL-13, and interferon
(IFN)- on barrier function and wound healing in Calu-3 human lung
epithelial cells. IL-4 and IL-13 treatment of Calu-3 cells grown on
Transwell filters resulted in a 70-75% decrease in barrier
function as assessed by electrophysiological and
[ 14 C]mannitol flux measurements. In contrast, IFN-
enhanced barrier function threefold using these same parameters. Cells
treated concurrently with IFN- and IL-4 or IL-13 showed an initial
decline in barrier function that was reversed within 2 days, resulting in barrier levels comparable to control cells. Analysis of the tight
junction-associated proteins ZO-1 and occludin showed that IL-4 and
IL-13 significantly reduced ZO-1 expression and modestly decreased
occludin expression compared with controls. IFN- , quite unexpectedly
given its enhancing effect on barrier function, reduced expression of
ZO-1 and occludin to almost undetectable levels compared with controls.
In wound-healing assays of cells grown on collagen I, IL-4 and IL-13
decreased migration, whereas IFN- treatment enhanced migration,
compared with control cells. Addition of IFN- , in combination with
IL-4 or IL-13, restored migration of cells to control levels. Migration
differences observed between the various cytokine treatments was
correlated with expression of the collagen I-binding
2 1 -integrin at the leading edge of cells
at the wound front; 2 1 -integrin
expression was decreased in IFN- -treated cells compared with
controls, whereas it was highest in IL-4- and IL-13-treated cells.
These results demonstrate that IL-4 and IL-13 diminish the capacity of
Calu-3 cells to maintain barrier function and repair wounds, whereas
IFN- promotes epithelial restitution by enhancing barrier function
and wound healing.
asthma; tight junctions; cell migration |
| doi_str_mv | 10.1152/ajpcell.2001.281.6.C2029 |
| format | Article |
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Immunex Corporation, Seattle, Washington 98101
To understand the
effects of cytokines on epithelial cells in asthma, we have
investigated the effects of interleukin (IL)-4, IL-13, and interferon
(IFN)- on barrier function and wound healing in Calu-3 human lung
epithelial cells. IL-4 and IL-13 treatment of Calu-3 cells grown on
Transwell filters resulted in a 70-75% decrease in barrier
function as assessed by electrophysiological and
[ 14 C]mannitol flux measurements. In contrast, IFN-
enhanced barrier function threefold using these same parameters. Cells
treated concurrently with IFN- and IL-4 or IL-13 showed an initial
decline in barrier function that was reversed within 2 days, resulting in barrier levels comparable to control cells. Analysis of the tight
junction-associated proteins ZO-1 and occludin showed that IL-4 and
IL-13 significantly reduced ZO-1 expression and modestly decreased
occludin expression compared with controls. IFN- , quite unexpectedly
given its enhancing effect on barrier function, reduced expression of
ZO-1 and occludin to almost undetectable levels compared with controls.
In wound-healing assays of cells grown on collagen I, IL-4 and IL-13
decreased migration, whereas IFN- treatment enhanced migration,
compared with control cells. Addition of IFN- , in combination with
IL-4 or IL-13, restored migration of cells to control levels. Migration
differences observed between the various cytokine treatments was
correlated with expression of the collagen I-binding
2 1 -integrin at the leading edge of cells
at the wound front; 2 1 -integrin
expression was decreased in IFN- -treated cells compared with
controls, whereas it was highest in IL-4- and IL-13-treated cells.
These results demonstrate that IL-4 and IL-13 diminish the capacity of
Calu-3 cells to maintain barrier function and repair wounds, whereas
IFN- promotes epithelial restitution by enhancing barrier function
and wound healing.
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Immunex Corporation, Seattle, Washington 98101
To understand the
effects of cytokines on epithelial cells in asthma, we have
investigated the effects of interleukin (IL)-4, IL-13, and interferon
(IFN)- on barrier function and wound healing in Calu-3 human lung
epithelial cells. IL-4 and IL-13 treatment of Calu-3 cells grown on
Transwell filters resulted in a 70-75% decrease in barrier
function as assessed by electrophysiological and
[ 14 C]mannitol flux measurements. In contrast, IFN-
enhanced barrier function threefold using these same parameters. Cells
treated concurrently with IFN- and IL-4 or IL-13 showed an initial
decline in barrier function that was reversed within 2 days, resulting in barrier levels comparable to control cells. Analysis of the tight
junction-associated proteins ZO-1 and occludin showed that IL-4 and
IL-13 significantly reduced ZO-1 expression and modestly decreased
occludin expression compared with controls. IFN- , quite unexpectedly
given its enhancing effect on barrier function, reduced expression of
ZO-1 and occludin to almost undetectable levels compared with controls.
In wound-healing assays of cells grown on collagen I, IL-4 and IL-13
decreased migration, whereas IFN- treatment enhanced migration,
compared with control cells. Addition of IFN- , in combination with
IL-4 or IL-13, restored migration of cells to control levels. Migration
differences observed between the various cytokine treatments was
correlated with expression of the collagen I-binding
2 1 -integrin at the leading edge of cells
at the wound front; 2 1 -integrin
expression was decreased in IFN- -treated cells compared with
controls, whereas it was highest in IL-4- and IL-13-treated cells.
These results demonstrate that IL-4 and IL-13 diminish the capacity of
Calu-3 cells to maintain barrier function and repair wounds, whereas
IFN- promotes epithelial restitution by enhancing barrier function
and wound healing.
asthma; tight junctions; cell migration</description><subject>Asthma - immunology</subject><subject>Asthma - physiopathology</subject><subject>Biological Transport</subject><subject>Blood-Air Barrier - physiology</subject><subject>Cadherins - metabolism</subject><subject>Cell Movement - physiology</subject><subject>Humans</subject><subject>Integrins - metabolism</subject><subject>Interferon-gamma - metabolism</subject><subject>Interleukin-13 - pharmacology</subject><subject>Interleukin-4 - pharmacology</subject><subject>Lung - drug effects</subject><subject>Lung - physiology</subject><subject>Mannitol - metabolism</subject><subject>Membrane Proteins - metabolism</subject><subject>Microscopy, Confocal</subject><subject>Occludin</subject><subject>Phosphoproteins - metabolism</subject><subject>Receptors, Collagen</subject><subject>Receptors, Interleukin-4 - metabolism</subject><subject>Respiratory Mucosa - cytology</subject><subject>Respiratory Mucosa - drug effects</subject><subject>Respiratory Mucosa - physiology</subject><subject>Tumor Cells, Cultured</subject><subject>Wound Healing - physiology</subject><subject>Zonula Occludens-1 Protein</subject><issn>0363-6143</issn><issn>1522-1563</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kE1v1DAQhq2Kii6Fv1DlxC3BH8nE5oZWLFRa0Us5W44z2bhyPrATlf33ze4GFQ5c7JHmed-RHkISRjPGCv7JPI0Wvc84pSzjkmWQbTnl6opsljVPWQHiDdlQASIFlosb8i7GJ0ppzkG9JTeMgZIc-Ib4_dwfEhzd1KJ3xieVCcFhSJq5t5Mb-sT0dfI8zMvbovFuoU3ApEYb0ESsk-qY3O_T_MwtAxPnCfvW9HZd736kB9N15j25boyP-GH9b8nP3dfH7fd0__Dtfvtln9q8gCkFkBZUwwXWRWlEKWmFha0tq5RgRjRSCmmgtEKpAoxhFgBUDjU0UtU0B3FLPl56xzD8mjFOunPxJMz0OMxRl5wDK0q5gPIC2jDEGLDRY3CdCUfNqD6Z1qtpfTKtF9Ma9Nn0Er1bb8xVh_VrcFW7ANkFaN2hfXYB9dgeoxv8cDi-1v7T-Pn_gd3s_SP-nv4k_wrqsW7EC7KAn_8</recordid><startdate>20011201</startdate><enddate>20011201</enddate><creator>Ahdieh, Minoo</creator><creator>Vandenbos, Tim</creator><creator>Youakim, Adel</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20011201</creationdate><title>Lung epithelial barrier function and wound healing are decreased by IL-4 and IL-13 and enhanced by IFN-gamma</title><author>Ahdieh, Minoo ; Vandenbos, Tim ; Youakim, Adel</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c456t-668c69f23ed57a3780be5cdc1b931a3f8838a67c39956aa1c666946d6f89d0463</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Asthma - immunology</topic><topic>Asthma - physiopathology</topic><topic>Biological Transport</topic><topic>Blood-Air Barrier - physiology</topic><topic>Cadherins - metabolism</topic><topic>Cell Movement - physiology</topic><topic>Humans</topic><topic>Integrins - metabolism</topic><topic>Interferon-gamma - metabolism</topic><topic>Interleukin-13 - pharmacology</topic><topic>Interleukin-4 - pharmacology</topic><topic>Lung - drug effects</topic><topic>Lung - physiology</topic><topic>Mannitol - metabolism</topic><topic>Membrane Proteins - metabolism</topic><topic>Microscopy, Confocal</topic><topic>Occludin</topic><topic>Phosphoproteins - metabolism</topic><topic>Receptors, Collagen</topic><topic>Receptors, Interleukin-4 - metabolism</topic><topic>Respiratory Mucosa - cytology</topic><topic>Respiratory Mucosa - drug effects</topic><topic>Respiratory Mucosa - physiology</topic><topic>Tumor Cells, Cultured</topic><topic>Wound Healing - physiology</topic><topic>Zonula Occludens-1 Protein</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ahdieh, Minoo</creatorcontrib><creatorcontrib>Vandenbos, Tim</creatorcontrib><creatorcontrib>Youakim, Adel</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>American Journal of Physiology: Cell Physiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ahdieh, Minoo</au><au>Vandenbos, Tim</au><au>Youakim, Adel</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Lung epithelial barrier function and wound healing are decreased by IL-4 and IL-13 and enhanced by IFN-gamma</atitle><jtitle>American Journal of Physiology: Cell Physiology</jtitle><addtitle>Am J Physiol Cell Physiol</addtitle><date>2001-12-01</date><risdate>2001</risdate><volume>281</volume><issue>6</issue><spage>C2029</spage><epage>C2038</epage><pages>C2029-C2038</pages><issn>0363-6143</issn><eissn>1522-1563</eissn><abstract>Departments of Biomolecular Screening and Protein Chemistry,
Immunex Corporation, Seattle, Washington 98101
To understand the
effects of cytokines on epithelial cells in asthma, we have
investigated the effects of interleukin (IL)-4, IL-13, and interferon
(IFN)- on barrier function and wound healing in Calu-3 human lung
epithelial cells. IL-4 and IL-13 treatment of Calu-3 cells grown on
Transwell filters resulted in a 70-75% decrease in barrier
function as assessed by electrophysiological and
[ 14 C]mannitol flux measurements. In contrast, IFN-
enhanced barrier function threefold using these same parameters. Cells
treated concurrently with IFN- and IL-4 or IL-13 showed an initial
decline in barrier function that was reversed within 2 days, resulting in barrier levels comparable to control cells. Analysis of the tight
junction-associated proteins ZO-1 and occludin showed that IL-4 and
IL-13 significantly reduced ZO-1 expression and modestly decreased
occludin expression compared with controls. IFN- , quite unexpectedly
given its enhancing effect on barrier function, reduced expression of
ZO-1 and occludin to almost undetectable levels compared with controls.
In wound-healing assays of cells grown on collagen I, IL-4 and IL-13
decreased migration, whereas IFN- treatment enhanced migration,
compared with control cells. Addition of IFN- , in combination with
IL-4 or IL-13, restored migration of cells to control levels. Migration
differences observed between the various cytokine treatments was
correlated with expression of the collagen I-binding
2 1 -integrin at the leading edge of cells
at the wound front; 2 1 -integrin
expression was decreased in IFN- -treated cells compared with
controls, whereas it was highest in IL-4- and IL-13-treated cells.
These results demonstrate that IL-4 and IL-13 diminish the capacity of
Calu-3 cells to maintain barrier function and repair wounds, whereas
IFN- promotes epithelial restitution by enhancing barrier function
and wound healing.
asthma; tight junctions; cell migration</abstract><cop>United States</cop><pmid>11698262</pmid><doi>10.1152/ajpcell.2001.281.6.C2029</doi></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0363-6143 |
| ispartof | American Journal of Physiology: Cell Physiology, 2001-12, Vol.281 (6), p.C2029-C2038 |
| issn | 0363-6143 1522-1563 |
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| source | MEDLINE; American Physiological Society; EZB-FREE-00999 freely available EZB journals |
| subjects | Asthma - immunology Asthma - physiopathology Biological Transport Blood-Air Barrier - physiology Cadherins - metabolism Cell Movement - physiology Humans Integrins - metabolism Interferon-gamma - metabolism Interleukin-13 - pharmacology Interleukin-4 - pharmacology Lung - drug effects Lung - physiology Mannitol - metabolism Membrane Proteins - metabolism Microscopy, Confocal Occludin Phosphoproteins - metabolism Receptors, Collagen Receptors, Interleukin-4 - metabolism Respiratory Mucosa - cytology Respiratory Mucosa - drug effects Respiratory Mucosa - physiology Tumor Cells, Cultured Wound Healing - physiology Zonula Occludens-1 Protein |
| title | Lung epithelial barrier function and wound healing are decreased by IL-4 and IL-13 and enhanced by IFN-gamma |
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