Differential Signaling Patterns Of Stimulated Bone Marrow-Derived Dendritic Cells Under Alpha 1-Antitrypsin-Enriched Conditions

Dendritic cells (DCs) mature upon an inflammatory trigger. However, an inflammatory trigger can lead to a semimature phenotype, allowing DCs to evoke tolerance and expedite the resolution of inflammation. This duality likely involves context-dependent modulation of inflammatory signaling. Human alpha 1-antitrypsin (hAAT) promotes semimature DCs. We examined changes in a wide spectrum of signaling cascades in stimulated murine bone marrow-derived cells with hAAT. Upon stimulation by IL-1 beta+IFN gamma, hAAT-treated cells depicted an attenuated calcium flux. Disrupting PKA or NF-kappa B pathways revoked only some hAAT-mediated outcomes. hAAT-treated cells exhibited a distict pattern of kinase phosphorylation. hAAT-mediated increase in Treg cells invitro required intact inflammatory signaling pathways. Taken together, hAAT appears to require a stimulated microenvironment to promote inflammatory resolution, setting it aside from classical anti-inflammatory agents. Further studies are required to identify the specific molecules targeted by hAAT that mediate these and other outcomes.