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Regulated production of interferon-inducible T-cell chemoattractants by human intestinal epithelial cells. Gastroenterology 2001 Jan;120(1):49-59

Date

02/24/2001

Pubmed ID

11208713

DOI

10.1053/gast.2001.20914

Scopus ID

2-s2.0-0035165138   174 Citations

Abstract

BACKGROUND & AIMS: Human intestinal epithelial cells inducibly express neutrophil and monocyte chemoattractants, yet little is known about the regulated production of T-cell chemoattractants by the intestinal epithelium. IP-10, Mig, and I-TAC are 3 CXC chemokines that are known to act as CD4(+) T-cell chemoattractants.

METHODS: We studied constitutive chemokine expression in human colon, and defined the regulated expression of these chemokines by reverse-transcription polymerase chain reaction, enzyme-linked immunosorbent assay, and immunohistology using cultured human intestinal epithelial cell lines and a novel adaptation of an in vivo human intestinal xenograft model.

RESULTS: IP-10 and Mig were constitutively expressed by normal human colon epithelium, and their cognate receptor, CXCR3, was expressed by mucosal mononuclear cells. Interferon (IFN)-gamma stimulation increased mRNA expression and the polarized basolateral secretion of these chemokines by human colon epithelial cell lines; infection with enteroinvasive bacteria, or stimulation with the proinflammatory cytokines tumor necrosis factor alpha and interleukin 1alpha, strongly potentiated IFN-gamma-induced epithelial cell IP-10, Mig, and I-TAC production. Epithelial cell mRNA and protein expression of IP-10, Mig, and I-TAC were rapidly up-regulated in human intestinal xenografts in response to stimulation with IFN-gamma alone or in combination with IL-1.

CONCLUSIONS: The constitutive and regulated production of the IFN-gamma-inducible chemokines IP-10, Mig, and I-TAC by human intestinal epithelium, and the expression of their cognate receptor, CXCR3, by mucosal mononuclear cells, suggest that the intestinal epithelium can play a role in modulating physiologic and pathologic T cell-mediated mucosal inflammation.

Author List

Dwinell MB, L├╝gering N, Eckmann L, Kagnoff MF

Author

Michael B. Dwinell PhD Director, Professor in the Microbiology and Immunology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Antineoplastic Agents
Bacterial Infections
CD4-Positive T-Lymphocytes
Chemokine CXCL10
Chemokine CXCL11
Chemokine CXCL9
Chemokines, CXC
Chemotaxis, Leukocyte
Enteritis
Fetal Tissue Transplantation
Fetus
Gene Expression
HT29 Cells
Humans
Intercellular Signaling Peptides and Proteins
Interferon-gamma
Interleukin-13
Interleukin-4
Intestinal Mucosa
Mice
Mice, Inbred C57BL
Mice, SCID
Neoplasm Transplantation
RNA, Messenger
Receptors, CXCR3
Receptors, Chemokine
Transplantation, Heterologous