PMID:11698262

Citation	Ahdieh, M, Vandenbos, T and Youakim, A (2001) Lung epithelial barrier function and wound healing are decreased by IL-4 and IL-13 and enhanced by IFN-gamma. Am. J. Physiol., Cell Physiol. 281:C2029-38
Abstract	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)-gamma 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-gamma enhanced barrier function threefold using these same parameters. Cells treated concurrently with IFN-gamma 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-gamma, 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-gamma treatment enhanced migration, compared with control cells. Addition of IFN-gamma, 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 alpha(2)beta(1)-integrin at the leading edge of cells at the wound front; alpha(2)beta(1)-integrin expression was decreased in IFN-gamma-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-gamma promotes epithelial restitution by enhancing barrier function and wound healing.
Links	PubMed
Keywords	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
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:IFNG	involved_in	GO:0010634: positive regulation of epithelial cell migration	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:IFNG		GO:0010634: positive regulation of epithelial cell migration	ECO:0000314:		P		Based of figure 7 and figure 8 wound healing of Calu-3 epithelial lung cells is enhanced by Interferon (IFN)-γ (Interferon gamma).	complete CACAO 6416
HUMAN:IL13		GO:0044319:	ECO:0000314:				Based on Figure 7 and Figure 8 wound-healing of Calu-3 epithelial lung cells is reduced by Interleukin-13 (IL-13).	complete
HUMAN:IL4		GO:0010633: negative regulation of epithelial cell migration	ECO:0000314:		P		Figure 7 shows that Interleukin-4 (IL-4) inhibits the migration of the Calu-3 epithelial cells, but it does not directly prove the inhibition of wound healing.	complete CACAO 6412
HUMAN:IL4	involved_in	GO:0010633: negative regulation of epithelial cell migration	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete

References

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