Interleukin-15 interactions with interleukin-15 receptor complexes: characterization and species specificity.

Interleukin (IL-) 2 and IL-15 share the IL-2 receptor betagamma c subunits (IL-2Rbetagamma c) but have specific, unique alpha receptor subunits. We studied species specificity of human (hu), simian (si), and mouse (mu) IL-15 and found that hu and si IL-15 behaved similarly in all systems investigated. Hu and mu IL-15 bound hu or mu IL-15Ralpha with equal high affinity in the presence or absence of IL-2Rbetagamma c and exhibited similar proliferative activities on cells containing all three subunits.

Lung epithelial barrier function and wound healing are decreased by IL-4 and IL-13 and enhanced by IFN-gamma.

To understand the effects of cytokines on epithelial cells in asthma, we have investigated the effects of interleukin (IL)-4, IL-13, and interferon (IFN)-gamma on barrier function and wound healing in Calu-3 human lung epithelial cells. IL-4 and IL-13 treatment of Calu-3 cells grown on Transwell filters resulted in a 70-75% decrease in barrier function as assessed by electrophysiological and [(14)C]mannitol flux measurements. In contrast, IFN-gamma enhanced barrier function threefold using these same parameters.

Interferon-gamma decreases barrier function in T84 cells by reducing ZO-1 levels and disrupting apical actin.

The effects of interferon-gamma (IFN-gamma) on tight junctions in T84 human intestinal epithelial cells were investigated. Treatment of T84 cells with IFN-gamma caused a dose- and time-dependent increase in monolayer permeability as assessed by transepithelial electrical resistance measurements. Examination of specific proteins associated with tight junctions by immunoblotting and confocal microscopy revealed changes in the expression levels and localization of some of these proteins after exposure of the cells to IFN-gamma.

Interleukin-15 up-regulates interleukin-2 receptor alpha chain but down-regulates its own high-affinity binding sites on human T and B cells.

The cytokines interleukin (IL)-2 and IL-15 share many biological activities as a consequence of their utilization of the beta and gamma chains of the IL-2 receptor. However, each cytokine binds to a specific receptor alpha chain; IL-2 with low affinity and IL-15 with high affinity. Here, we demonstrate that IL-15, like IL-2, up-regulates expression of IL-2R alpha on human T and B cells, but rapidly down-regulates IL-15 high-affinity binding sites, which represent IL-15R alpha.

Functional characterization of the human interleukin-15 receptor alpha chain and close linkage of IL15RA and IL2RA genes.

Interleukins-2 and -15 (IL-2 and IL-15) are cytokines with overlapping but distinct biological effects. Their receptors share two subunits (the IL-2R beta and -gamma chains) that are essential for signal transduction. The IL-2 receptor requires an additional IL-2-specific alpha subunit for high affinity IL-2 binding.