Background and Purpose: Macrophage infiltration and activation is a critical step during acute pancreatitis (AP). We have shown that pancreas-specific D 2 receptor signalling protects against AP severity. As it is unclear to what extent myeloidspecific D 2 receptor mediates AP, we investigated the role of myeloid-specific D 2 receptor signalling in AP. Experimental Approach: Using wild-type and LysM +/cre D 2 fl/fl mice, AP was induced by L-arginine, caerulein and LPS. Murine bone marrow-derived macrophages and human peripheral blood mononuclear cells (PBMCs) were isolated, cultured and then induced to M1 phenotype. AP severity was assessed by measurements of serum amylase and lipase and histological grading. Macrophage phenotype was assessed by flow cytometry and qRT-PCR. NADPH oxidase-induced oxidative stress and NF-κB and NLRP3 inflammasome signalling pathways were also evaluated.Key Results: We found that dopaminergic system was activated and dopamine reduced inflammatory cytokine expression in M1-polarized macrophages from human PBMCs. Dopaminergic synthesis was also activated, but D 2 receptor expression was down-regulated in M1-polarized macrophages from murine bone marrows.During AP, myeloid-specific D 2 receptor deletion worsened pancreatic injury, systematic inflammation and promoted macrophages to M1 phenotype. Furthermore, M1 macrophages from LysM +/cre D 2 fl/fl mice exhibited increased NADPH oxidaseinduced oxidative stress and enhanced NF-κB and NLRP3 inflammasome activation. D 2 receptor activation inhibited M1 macrophage polarization, oxidative stressinduced NF-κB and NLRP3 inflammasome activation.Conclusion and Implications: Our data for the first time showed that myeloidspecific D 2 receptor signalling controls pancreatic injury and systemic inflammation via inhibiting M1 macrophage, suggesting D 2 receptor activation might serve as therapeutic target for AP.
SUPPORTING INFORMATIONAdditional supporting information may be found online in the Supporting Information section at the end of this article.How to cite this article: Han X, Ni J, Wu Z, et al. Myeloidspecific dopamine D 2 receptor signalling controls inflammation in acute pancreatitis via inhibiting M1 macrophage. Br
α-Amino imides can be accessed straightforwardly from tertiary amines through copper-catalyzed three-component reactions involving the direct functionalization of sp(3) C-Hs adjacent to nitrogen atoms. This reaction has demonstrated a tolerance to a wide range of functionalizations and can be performed under very mild conditions. A plausible mechanism has been proposed in which an Ugi-type cascade assembly has been included.
Cholesterol gallstone (CGS) disease is prevalent worldwide. None of the medical options for prevention and treatment of CGS disease are recommended, and surgical management has a high rate of recurrence.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.