Cytokine-induced upregulation of NF-kappaB, IL-8, and ICAM-1 is dependent on colonic cell polarity: implication for PKCdelta.
As described for a long time, carcinoma-derived Caco-2 cells form a polarized epithelium in culture, whereas HT29-D4 cells are nonpolarized and undifferentiated but can form a polarized monolayer when cultured in a galactose-supplemented medium. Using NF-kappaB translocation and IL-8 and ICAM-1 gene activation as an index, we have studied the relationship between the differentiation state and the cell response to cytokines. We found that differentiated Caco-2 and HT29-D4 cells were responsive to both cytokines TNFalpha- and IL-1beta-mediated activation of NF-kappaB but that undifferentiated HT29-D4 cells were unresponsive to IL-1beta. However, the expression of endogenous ICAM-1 and IL-8 genes was upregulated by these cytokines in either cell lines differentiated or not. Upregulation of ICAM-1 gene occurred when IL-1beta or TNFalpha was added to the basal, but not apical surface of the differentiated epithelia. Finally, it appeared that in polarized HT29-D4 cells, the IL-1beta-induced translocation of NF-kappaB was connected to PKCdelta translocation.
Vallee
Sebastien
S
Laboratoire de Biochimie Cellulaire, Faculté de Pharmacie, UMR 6032 CNRS, FR-13385 Marseille Cedex, France.
Laforest
Sullivan
S
Fouchier
Francis
F
Montero
Marie Pierre
MP
Penel
Claude
C
Champion
Serge
S
D000230:Adenocarcinoma / Q000201:enzymology / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology / Q000235:genetics; D016764:Cell Polarity / Q000187:drug effects / Q000502:physiology*; D003110:Colonic Neoplasms / Q000201:enzymology / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000378:metabolism* / Q000494:pharmacology; D004361:Drug Tolerance / Q000235:genetics; D004847:Epithelial Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000235:genetics; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D007375:Interleukin-1 / Q000378:metabolism / Q000494:pharmacology; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D008871:Microvilli / Q000187:drug effects / Q000201:enzymology / Q000235:genetics; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D051745:Protein Kinase C-delta; D021381:Protein Transport / Q000187:drug effects / Q000235:genetics; D015533:Transcriptional Activation; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
D016207:Cytokines; D007375:Interleukin-1; D016209:Interleukin-8; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; C497258:PRKCD protein, human; D011493:Protein Kinase C; D051745:Protein Kinase C-delta