Interleukin-4 and interferon-gamma synergistically increase secretory component gene expression, but are additive in stimulating secretory immunoglobulin A release by Calu-3 airway epithelial cells

Interleukin-4 (IL-4) and interferon-gamma (IFN-gamma) synergize to express polymeric immunoglobulin receptor (pIgR) but their combined effect, and tha t of IL-4 alone, on secretory immunoglobulin A (sIgA) release is unknown. R ecently, we have developed an airway epithelial cell model that allows asse ssment of the integrated effect of a stimulus on pIgR gene and protein expr ession and sIgA release. With this model we show here that IL-4 and IFN-gam ma dose-dependently increased pIgR mRNA and protein expression, and sIgA re lease. IFN-gamma and IL-4 induced similar maximal expression of pIgR, but I FN-gamma enhanced sIgA release more than IL-4. When added together, IL-4 an d IFN-gamma synergistically increased pIgR mRNA and protein expression, but sIgA release was stimulated in an additive manner. Thus, IL-4 and IFN-gamm a may be implicated in the increase of sIgA levels as found in mucosal infl ammatory diseases. In addition, our results indicate that transport and rel ease of empty pIgR is subject to regulatory mechanisms different from those of pIgR with bound dimeric IgA.