Ubiquitous production of macrophage migration inhibitory factor by human gastric and intestinal epithelium.
OBJECTIVE
Macrophage migration inhibitory factor (MIF) inhibits macrophage migration and has pleiotropic activities on immune and inflammatory responses, cell growth, and glucose metabolism. MIF is produced by T cells, macrophages, and endothelial cells. Because intestinal epithelial cells produce mediators important for regulating mucosal immune and inflammatory responses, we sought to determine if these cells produce MIF.


METHODS
MIF expression was determined by immunostaining of human intestinal mucosa, intestinal xenografts, and cultured cells. MIF protein levels were quantitated by enzyme-linked immunosorbent assay and immunoblot analysis, messenger RNA was assessed by real-time reverse-transcription polymerase chain reaction, and functional activity was assessed by enzymatic and migration assays.


RESULTS
MIF was abundantly expressed in vivo in gastric, small intestinal, and colonic epithelium and in epithelium lining human intestinal xenografts. MIF was also constitutively expressed at the messenger RNA and protein level by several cultured colon and gastric epithelial cell lines, and its expression in those cells was not up-regulated by the proinflammatory cytokines interleukin 1alpha, tumor necrosis factor alpha, or interferon gamma. Epithelial MIF from cultured cells was released predominantly from the apical side after Salmonella infection, had tautomerase activity, and arrested macrophage migration.


CONCLUSIONS
Human intestinal epithelial cells are a major source of MIF, a molecule that can regulate macrophage migration, inflammation, and cell metabolism.
Maaser
Christian
C
Laboratory of Mucosal Immunology, Department of Medicine, University of California, San Diego, La Jolla, California 92093-0623, USA.
Eckmann
Lars
L
Paesold
Günther
G
Kim
Hyun S
HS
Kagnoff
Martin F
MF
D000818:Animals; D018938:Caco-2 Cells; D002465:Cell Movement / Q000276:immunology; D016764:Cell Polarity / Q000502:physiology; D004751:Enteritis / Q000473:pathology / Q000503:physiopathology; D005753:Gastric Mucosa / Q000166:cytology / Q000276:immunology* / Q000382:microbiology; D015870:Gene Expression / Q000276:immunology; D019073:HT29 Cells; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology* / Q000382:microbiology; D008263:Macrophage Migration-Inhibitory Factors / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D009000:Monocytes / Q000166:cytology / Q000276:immunology; D010667:Phenylpyruvic Acids / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D012480:Salmonella Infections / Q000473:pathology / Q000503:physiopathology; D014183:Transplantation, Heterologous
D008263:Macrophage Migration-Inhibitory Factors; D010667:Phenylpyruvic Acids; D012333:RNA, Messenger; C010590:4-hydroxyphenylpyruvic acid