Enterocytes are the primary source of the chemokine ENA-78 in normal colon and ulcerative colitis.
Epithelial cell-derived neutrophil-activating protein-78 (ENA-78) is a neutrophil-directed C-X-C chemokine. We report that Caco-2 and T84 human intestinal epithelial cells produce ENA-78 after stimulation by interleukin (IL)-1 beta or tumor necrosis factor-alpha. Caco-2 cells show increased IL-8 production at 4-12 h and increased ENA-78 production at 8-24 h after cytokine stimulation. Immunohistochemical studies in normal human colon and in ulcerative colitis demonstrate ENA-78 immunoreactivity principally associated with crypt epithelial cells. Furthermore, human colonic tissues from patients with ulcerative colitis show elevated levels of ENA-78 mRNA (24-fold increase, P < 0.01) and protein (4-fold increase, P < 0.05) compared with normal controls. Thus ENA-78 is produced in normal colon and in ulcerative colitis and is predominantly of enterocyte origin. The kinetics of ENA-78 induction in human colon epithelial cell lines are delayed and prolonged compared with IL-8. We propose that ENA-78 and IL-8 serve complementary and sequential roles in neutrophil recruitment in ulcerative colitis. ENA-78 as an enterocyte-derived, neutrophil-activating chemokine may be especially important in neutrophil recruitment from the lamina propria into the epithelial layer.
Keates
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Gastroenterology Division, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA.
Keates
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AC
Mizoguchi
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Bhan
A
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Kelly
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CP
D002460:Cell Line; D054365:Chemokine CXCL5; D019743:Chemokines, CXC; D003093:Colitis, Ulcerative / Q000276:immunology* / Q000473:pathology; D003106:Colon / Q000166:cytology / Q000276:immunology* / Q000473:pathology; D003110:Colonic Neoplasms; D003424:Crohn Disease / Q000276:immunology; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000494:pharmacology; D016209:Interleukin-8 / Q000031:analogs & derivatives* / Q000032:analysis / Q000096:biosynthesis*; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology* / Q000473:pathology; D016133:Polymerase Chain Reaction; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D015398:Signal Transduction; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
C486263:CXCL5 protein, human; D054365:Chemokine CXCL5; D019743:Chemokines, CXC; D017931:DNA Primers; D007375:Interleukin-1; D016209:Interleukin-8; D012333:RNA, Messenger