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Gut. 1998 Feb; 42(2): 208–213.
PMCID: PMC1726988

Interferon γ induces differential upregulation of α and β chemokine secretion in colonic epithelial cell lines

Abstract

Background—Production of chemoattractant factors by the intestinal epithelium may contribute to mucosal infiltration by inflammatory cells in inflammatory bowel disease. Secretion of the α chemokine interleukin 8 (IL-8), a neutrophil chemoattractant, has been widely studied, but little is known about epithelial secretion of β chemokines, which are preferentially involved in recruiting monocytes. 
Aims—To investigate the profiles of α and β chemokine secretion in colonic cell lines and their differential modulation by interferon γ (IFN-γ), a product of activated T lymphocytes and natural killer cells. 
Methods and results—HT29-19A, a model of the Cl secretory crypt cell, exhibited a parallel secretion of the α chemokines IL-8 and GROα, which could be markedly upregulated by tumour necrosis factor α (TNF-α) and IL-1β. These cells showed no significant expression of the β chemokines RANTES (regulated upon activation T cell expressed and secreted), MIP-1α (macrophage inflammatory protein 1α), and MCP-1 (monocyte chemotactic protein 1) under these conditions, but IFN-γ in combination with TNF-α caused a dose dependent induction of RANTES and MCP-1 secretion. This was accompanied by a marked increase of RANTES mRNA. In contrast, IFN-γ had no significant effect on TNF-α stimulated IL-8 secretion. Caco-2 cells, with features more typical of villus absorptive cells, were relatively poor secretors of α chemokines but secreted high levels of MCP-1 in response to IL-1β. IFN-γ did not influence α or β chemokine secretion in these cells. 
Conclusions—These studies suggest that intestinal epithelial cells may produce chemokines capable of attracting both neutrophils and monocytes. The ability of IFN-γ to activate the expression of β chemokines preferentially could facilitate the development of chronic inflammatory infiltrates. 



Keywords: inflammatory bowel disease; RANTES; interferon gamma; chemokine

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Selected References

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Figures and Tables

Figure 1
Secretion of α and β chemokines in (A) HT29-19A and (B) Caco-2 human colonic cell lines. Cultures were incubated for 24 hours with control media alone or in the presence of TNF-α (2 ng/ml in HT29-19A and 50 ng/ml in Caco-2), IL-1 ...
Figure 2
Dose dependent stimulation of α chemokine secretion by IL-1 in HT29-19A and Caco-2 cells. Chemokine levels were measured 24 hours after addition of IL-1 to confluent cultures. Values are mean (SEM) for 3-8 observations in each group. ...
Figure 3
Influence of IFN-γ on basal and TNF-α stimulated secretion of α and β chemokines in HT29-19A cells. Chemokines were measured 24 hours after incubation with control media or 50 ng/ml TNF-α in the presence or absence ...
Figure 4
Synergistic effect of TNF-α and IFN-γ on RANTES mRNA expression in the HT29-19A cell line. Cells were incubated with TNF-α alone (50 ng/ml), IFN-γ alone (50 IU/ml), or TNF-α + IFN-γ for 24 hours. The expression ...
Figure 5
Dose dependence of RANTES secretion in response to combinations of TNF-α and IFN-γ in the HT29-19A cell line. Cells were incubated with varying concentrations of TNF-α, either alone or in the presence of 10 or 50 U/ml IFN-γ ...
Figure 6
Effect of TNF-α and IFN-γ on vectorial secretion of chemokines from polarised HT29-19A monolayers. Cells were grown to confluency on Transwell filter supports and the integrity of the resulting monolayer checked by monitoring development ...

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