Th2- and to a lesser extent Th1-type cytokines upregulate the production of both CXC (IL-8 and gro-alpha) and CC (RANTES, eotaxin, eotaxin-2, MCP-3 and MCP-4) chemokines in human airway epithelial cells.

BACKGROUND

Both CXC and CC chemokines play an important role in leukocyte recruitment. However, a systematic examination of their production by human airway epithelial cells (HAECs) has not been carried out. The objective of this study was to investigate whether Th1- and Th2-type cytokines regulate chemokine production in HAECs.

METHODS

HAECs were grown from both nasal and bronchial tissue and subsequently stimulated with either Th1- or Th2-type cytokines.

RESULTS

Constitutive mRNA expression for gro-alpha, IL-8 and RANTES was seen in both human nasal and human bronchial epithelial cells. IL-4 was the strongest stimulus for both gene expression and protein production of the chemokines RANTES, IL-8 and gro-alpha, while both IL-13 and IFN-gamma were weaker inducers of these chemokines, with the exception of gro-alpha (IL-13 was a strong stimulus for gro-alpha production). TNF-alpha synergized with IL-4, and to a lesser extent with IFN-gamma and IL-13, to release RANTES, IL-8 and gro-alpha. IL-4 and to a lesser extent IL-13 and IFN-gamma stimulated the production of MCP-3 and -4, eotaxin and eotaxin-2 immunoreactivities. However, no induction of the mRNAs encoding these chemokines was observed, suggesting that they may be released from a preformed pool within the HAECs.

CONCLUSION

These findings suggest that when released into the airways, Th2- and to a lesser extent Th1-type cytokines may stimulate recruitment of eosinophils and neutrophils through the release of CC (RANTES, MCP-3 and -4, eotaxin and eotaxin-2) and CXC chemokines (gro-alpha and IL-8).