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Am J Physiol Gastrointest Liver Physiol 280: G1217-G1226, 2001;
0193-1857/01 $5.00
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Vol. 280, Issue 6, G1217-G1226, June 2001

Production of MDC/CCL22 by human intestinal epithelial cells

M. Cecilia Berin, Michael B. Dwinell, Lars Eckmann, and Martin F. Kagnoff

Laboratory of Mucosal Immunology, Department of Medicine, University of California at San Diego, La Jolla, California 92093

The intestinal mucosa contains a subset of lymphocytes that produce Th2 cytokines, yet the signals responsible for the recruitment of these cells are poorly understood. Macrophage-derived chemokine (MDC/CCL22) is a recently described CC chemokine known to chemoattract the Th2 cytokine producing cells that express the receptor CCR4. The studies herein demonstrate the constitutive production of MDC/CCL22 in vivo by human colon epithelium and by epithelium of human intestinal xenografts. MDC/CCL22 mRNA expression and protein secretion was upregulated in colon epithelial cell lines in response to proinflammatory cytokines or infection with enteroinvasive bacteria. Inhibition of nuclear factor (NF)-kappa B activation abolished MDC/CCL22 expression in response to proinflammatory stimuli, demonstrating that MDC/CCL22 is a NF-kappa B target gene. In addition, tumor necrosis factor-alpha -induced MDC/CCL22 secretion was differentially modulated by Th1 and Th2 cytokines. Supernatants from the basal, but not apical, side of polarized epithelial cells induced a MDC/CCL22-dependent chemotaxis of CCR4-positive T cells. These studies demonstrate the constitutive and regulated production by intestinal epithelial cells of a chemokine known to function in the trafficking of T cells that produce anti-inflammatory cytokines.

mucosa; cytokines; Th1/Th2; chemotaxis


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