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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


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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