Neuropeptide Y induces secretion of high-mobility group box 1 protein in mouse macrophage via PKC/ERK dependent pathway

• NPY directly potentiates the HMGB1 release from macrophage.
• NPY-induced HMGB1 release in macrophage is active release.
• PKC and ERK pathway are involved in the NPY-induced HMGB1 release.

Despite increasing evidence highlighting the role of NPY in the modulation of inflammatory reaction, surprisingly little is known about the direct effects of NPY on the release of proinflammatory mediators. In the present work, we have evaluated the effects of NPY on the release of TNF-α, IL-1β, IL-6 and HMGB1 mediators in peritoneal macrophages. Our results demonstrate for the first time that NPY can directly induce active HMGB1 release and cytoplasmic translocation, while the production of TNF-α, IL-1β and IL-6 is not affected. PKC and ERK pathway inhibitors can abolish the promotive effect of NPY on HMGB1 secretion. Thus, our results indicate that NPY might impact on the innate immune system by directly potentiating the HMGB1 release from the macrophage.