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Regulated MIP-3alpha/CCL20 production by human intestinal epithelium: mechanism for modulating mucosal immunity. Am J Physiol Gastrointest Liver Physiol 2001 Apr;280(4):G710-9

Date

03/20/2001

Pubmed ID

11254498

DOI

10.1152/ajpgi.2001.280.4.G710

Scopus ID

2-s2.0-0035013827   204 Citations

Abstract

Human intestinal epithelial cells secrete an array of chemokines known to signal the trafficking of neutrophils and monocytes important in innate mucosal immunity. We hypothesized that intestinal epithelium may also have the capacity to play a role in signaling host adaptive immunity. The CC chemokine macrophage inflammatory protein (MIP)-3alpha/CCL20 is chemotactic for immature dendritic cells and CD45RO(+) T cells that are important components of the host adaptive immune system. In these studies, we demonstrate the widespread production and regulated expression of MIP-3alpha by human intestinal epithelium. Several intestinal epithelial cell lines were shown to constitutively express MIP-3alpha mRNA. Moreover, MIP-3alpha mRNA expression and protein production were upregulated by stimulation of intestinal epithelial cells with the proinflammatory cytokines tumor necrosis factor-alpha or interleukin-1alpha or in response to infection with the enteric bacterial pathogens Salmonella or enteroinvasive Escherichia coli. In addition, MIP-3alpha was shown to function as a nuclear factor-kappaB target gene. In vitro findings were paralleled in vivo by increased expression of MIP-3alpha in the epithelium of cytokine-stimulated or bacteria-infected human intestinal xenografts and in the epithelium of inflamed human colon. Mucosal T cells, other mucosal mononuclear cells, and intestinal epithelial cells expressed CCR6, the cognate receptor for MIP-3alpha. The constitutive and regulated expression of MIP-3alpha by human intestinal epithelium is consistent with a role for epithelial cell-produced MIP-3alpha in modulating mucosal adaptive immune responses.

Author List

Izadpanah A, Dwinell MB, Eckmann L, Varki NM, 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

Adenoviridae
Animals
Chemokine CCL20
Chemokines, CC
Enzyme-Linked Immunosorbent Assay
Epithelium
Fetal Tissue Transplantation
Humans
Immunity, Mucosal
Indicators and Reagents
Interleukin-1
Intestinal Mucosa
Macrophage Inflammatory Proteins
Mice
Mice, Inbred C57BL
Receptors, CCR6
Receptors, Chemokine
Repressor Proteins
Salmonella Infections
Transplantation, Heterologous
Tumor Cells, Cultured
Up-Regulation