CXCL8 modulates human intestinal epithelial cells through a CXCR1 dependent pathway.
BACKGROUND
CXCL8 (previously known as Interleukin-8), a member of the alpha-chemokine family of chemotactic cytokines, stimulates intestinal neutrophil activation and chemotaxis. As intestinal epithelial cells have been recently shown to produce CXCL8, the aim of this study was to identify functional activities of CXCL8 on intestinal epithelial cells.


METHODS
The expression of CXCL8 receptors CXCR1 and CXCR2 was assessed by RT-PCR and FACS analysis in human Caco-2 and HT-29 cells. The effects of CXCL8 on intestinal epithelial proliferation were assessed with colorimetric MTT assays and the effects on epithelial restitution with an in vitro migration model using Caco-2 and HT-29 cells.


RESULTS
While the expression of both CXCR1 mRNA and protein could be demonstrated by RT-PCR and FACS analysis in human Caco-2 and HT-29 cells, no expression of CXCR2 was observed in these cell lines. Colorimetric MTT assays revealed that CXCL8 does not modulate cell proliferation in HT-29 and Caco-2 cells. In contrast, CXCL8 significantly enhanced intestinal epithelial migration in an in vitro migration model of HT-29 and Caco-2 cells. Enhancement of intestinal epithelial cell migration by CXCL8 was partially CXCR1-dependent and TGFbeta-independent.


CONCLUSIONS
CXCL8 exerts functional effects on intestinal epithelial cells that may be relevant for intestinal inflammation and mucosal healing.
Sturm
Andreas
A
Department of Hepatology and Gastroenterology, Charité -- Universitätsmedizin Berlin, Campus Virchow, Augustenburger Platz 1, D-13353 Berlin, Germany.
Baumgart
Daniel C
DC
d'Heureuse
Johanna Harder
JH
Hotz
Angelika
A
Wiedenmann
Bertram
B
Dignass
Axel U
AU
D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002469:Cell Separation; D002633:Chemotaxis; D003106:Colon / Q000378:metabolism; D004396:Coloring Agents / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D007249:Inflammation; D016209:Interleukin-8 / Q000502:physiology*; D007413:Intestinal Mucosa / Q000378:metabolism; D009092:Mucous Membrane / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D023062:Receptors, Interleukin-8A / Q000378:metabolism*; D023063:Receptors, Interleukin-8B / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism
D004396:Coloring Agents; D016207:Cytokines; D016209:Interleukin-8; D012333:RNA, Messenger; D023062:Receptors, Interleukin-8A; D023063:Receptors, Interleukin-8B; D013778:Tetrazolium Salts; D013844:Thiazoles; D016212:Transforming Growth Factor beta; C022616:thiazolyl blue