The autonomic nervous system has been studied for its involvement in the control of macrophages; however, the mechanisms underlying the interaction between the adrenergic receptors and alternatively activated macrophages (M2) remain obscure. Using FVB wild-type and beta 2 adrenergic receptors knockout, we found that ß2-AR deficiency alleviates hepatobiliary damage in mice infected with C. sinensis. Moreover, ß2-AR-deficient mice decrease the activation and infiltration of M2 macrophages and decrease the production of type 2 cytokines, which are associated with a significant decrease in liver fibrosis in infected mice. Our in vitro results on bone marrow-derived macrophages revealed that macrophages from Adrb2-/- mice significantly decrease M2 markers and the phosphorylation of ERK/mTORC1 induced by IL-4 compared to that observed in M2 macrophages from Adrb2+/+ . This study provides a better understanding of the mechanisms by which the ß2-AR enhances type 2 immune response through the ERK/mTORC1 signaling pathway in macrophages and their role in liver fibrosis.
Clonorchiasis/complications , Liver Cirrhosis, Biliary/immunology , Liver Cirrhosis/immunology , Macrophage Activation , Neuroimmunomodulation/physiology , Receptors, Adrenergic, beta-2/physiology , Animals , Autonomic Nervous System/physiopathology , Bile Ducts/parasitology , Bile Ducts/pathology , Cells, Cultured , Clonorchiasis/immunology , Clonorchiasis/physiopathology , Cytokines/blood , Humans , Liver Cirrhosis/etiology , Liver Cirrhosis/parasitology , Liver Cirrhosis/pathology , Liver Cirrhosis, Biliary/etiology , Liver Cirrhosis, Biliary/parasitology , Liver Cirrhosis, Biliary/pathology , MAP Kinase Signaling System , Macrophages/classification , Macrophages/immunology , Male , Mechanistic Target of Rapamycin Complex 1/physiology , Mice, Knockout , Receptors, Adrenergic, beta-2/deficiency , Specific Pathogen-Free Organisms
S-palmitoylation is one of the most common post-translational modifications in nature; however, its importance has been overlooked for decades. Crohn's disease (CD), a subtype of inflammatory bowel disease (IBD), is an autoimmune disease characterized by chronic inflammation involving the entire gastrointestinal tract. Bowel damage and subsequent disabilities caused by CD are a growing global health issue. Well-acknowledged risk factors for CD include genetic susceptibility, environmental factors, such as a westernized lifestyle, and altered gut microbiota. However, the pathophysiological mechanisms of this disorder are not yet comprehensively understood. With the rapidly increasing global prevalence of CD and the evident role of S-palmitoylation in CD, as recently reported, there is a need to investigate the relationship between CD and S-palmitoylation. In this review, we summarize the concept, detection, and function of S-palmitoylation as well as its potential effects on CD, and provide novel insights into the pathogenesis and treatment of CD.
Crohn Disease , Gastrointestinal Microbiome , Inflammatory Bowel Diseases , Crohn Disease/diagnosis , Crohn Disease/epidemiology , Crohn Disease/genetics , Humans , Lipoylation
