Production of MDC/CCL22 by human intestinal epithelial cells.
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)-kappaB activation abolished MDC/CCL22 expression in response to proinflammatory stimuli, demonstrating that MDC/CCL22 is a NF-kappaB 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.
Berin
M C
MC
Laboratory of Mucosal Immunology, Department of Medicine, University of California at San Diego, La Jolla, CA 92093, USA.
Dwinell
M B
MB
Eckmann
L
L
Kagnoff
M F
MF
D000818:Animals; D016764:Cell Polarity / Q000502:physiology; D054422:Chemokine CCL22; D019742:Chemokines, CC / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D003106:Colon / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism / Q000494:pharmacology; D004927:Escherichia coli Infections / Q000378:metabolism; D016332:Fetal Tissue Transplantation; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism* / Q000382:microbiology; D007422:Intestines / Q000196:embryology / Q000637:transplantation; D051379:Mice; D016513:Mice, SCID; D016328:NF-kappa B / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D012480:Salmonella Infections / Q000378:metabolism; D013601:T-Lymphocytes / Q000502:physiology; D018418:Th2 Cells / Q000378:metabolism; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
C515482:CCL22 protein, human; C515483:Ccl22 protein, mouse; D054422:Chemokine CCL22; D019742:Chemokines, CC; D016207:Cytokines; D016328:NF-kappa B; D012333:RNA, Messenger