Dopamine-driven increase in IL-1β in myeloid cells is mediated by differential dopamine receptor expression and exacerbated by HIV

作者：Stephanie Matt, Rachel Nolan, Samyuktha Manikandan, Yash Agarwal, Breana Channer, Oluwatofunmi Oteju, Marzieh Daniali, Joanna Canagarajah, Teresa LuPone, Krisna Mompho, Kaitlyn Runner, Emily Nickoloff-Bybel, Benjamin Li, Meng Niu, Johannes C. M. Schlachetzki, Howard S. Fox, Peter J. Gaskill · 发表于：Journal of Neuroinflammation · 年份：2025 · DOI：10.1186/s12974-025-03403-9 · 被引用次数：11 · 研究领域：Tryptophan and brain disorders、Immune Cell Function and Interaction、Stress Responses and Cortisol

The catecholamine neurotransmitter dopamine is classically known for regulation of central nervous system (CNS) functions such as reward, movement, and cognition. Increasing evidence also indicates that dopamine regulates critical functions in peripheral organs and is an important immunoregulatory factor. We have previously shown that dopamine increases NF-κB activity, inflammasome activation, and the production of inflammatory cytokines such as IL-1β in human macrophages. As myeloid lineage cells are central to the initiation and resolution of acute inflammatory responses, dopamine-mediated dysregulation of these functions could both impair the innate immune response and exacerbate chronic inflammation. However, the exact pathways by which dopamine drives myeloid inflammation are not well defined, and studies in both rodent and human systems indicate that dopamine can impact the production of inflammatory mediators through both D1-like dopamine receptors (DRD1, DRD5) and D2-like dopamine receptors (DRD2, DRD3, and DRD4). Therefore, we hypothesized that dopamine-mediated production of IL-1β in myeloid cells is regulated by the ratio of different dopamine receptors that are activated. Our data in primary human monocyte-derived macrophages (hMDM) indicate that DRD1 expression is necessary for dopamine-mediated increases in IL-1β, and that changes in the expression of DRD2 and other dopamine receptors can alter the magnitude of the dopamine-mediated increase in IL-1β. Mature hMD...