1.Upregulation of FcγRIIB by resveratrol via NF-κB activation reduces B-cell numbers and ameliorates lupus.
Jyun Pei JHOU ; Se Jie CHEN ; Ho Yin HUANG ; Wan Wan LIN ; Duen Yi HUANG ; Shiang Jong TZENG
Experimental & Molecular Medicine 2017;49(9):e381-
Resveratrol, an anti-inflammatory agent, can inhibit pro-inflammatory mediators by activating Sirt1, which is a class III histone deacetylase. However, whether resveratrol can regulate inhibitory or anti-inflammatory molecules has been less studied. FcγRIIB, a receptor for IgG, is an essential inhibitory receptor of B cells for blocking B-cell receptor-mediated activation and for directly inducing apoptosis of B cells. Because mice deficient in either Sirt1 or FcγRIIB develop lupus-like diseases, we investigated whether resveratrol can alleviate lupus through FcγRIIB. We found that resveratrol enhanced the expression of FcγRIIB in B cells, resulting in a marked depletion of plasma cells in the spleen and notably in the bone marrow, thereby decreasing serum autoantibody titers in MRL/lpr mice. The upregulation of FcγRIIB by resveratrol involved an increase of Sirt1 protein and deacetylation of p65 NF-κB (K310). Moreover, increased binding of phosphor-p65 NF-κB (S536) but decreased association of acetylated p65 NF-κB (K310) and phosphor-p65 NF-κB (S468) to the −480 promoter region of Fcgr2b gene was responsible for the resveratrol-mediated enhancement of FcγRIIB gene transcription. Consequently, B cells, especially plasma cells, were considerably reduced in MRL/lpr mice, leading to improvement of nephritis and prolonged survival. Taken together, we provide evidence that pharmacological upregulation of FcγRIIB expression in B cells via resveratrol can selectively reduce B cells, decrease serum autoantibodies and ameliorate lupus nephritis. Our findings lead us to propose FcγRIIB as a new target for therapeutic exploitation, particularly for lupus patients whose FcγRIIB expression levels in B cells are downregulated.
Animals
;
Apoptosis
;
Autoantibodies
;
B-Lymphocytes*
;
Bone Marrow
;
Histone Deacetylases
;
Humans
;
Immunoglobulin G
;
Lupus Nephritis
;
Mice
;
Nephritis
;
Plasma Cells
;
Promoter Regions, Genetic
;
Spleen
;
Up-Regulation*
2. Utilization of hospital service and its influencing factors among patients with occupational pneumoconiosis
Mei-xiong LI ; Shao-se YE ; Zhong-xue LI ; Kang-cheng CHEN ; Fang-hua LI ; Jie LI ; Yu ZHANG
China Occupational Medicine 2021;48(04):402-406
OBJECTIVE: To analyze the utilization of hospital service and its related influencing factors among patients with occupational pneumoconiosis. METHODS: A total of 178 patients with occupational pneumoconiosis were selected as the study subjects using the convenience sampling method. The utilization of hospital service and health-related quality of life of patients with pneumoconiosis and its complications were investigated using the Questionnaire on Pneumoconiosis Patients′ Medical Consultation Behavior and its Influencing Factors and the European Quality of Life Inventory.RESULTS: The one-year hospitalization rate of patients with pneumoconiosis was 57.3%(102/178), and 88.2% of the patients were hospitalized once a year. The median number of hospitalization time in a year was 20.0 days. Visual health scale(VAS) score was(58±15) points. The multiple logistic regression analysis results showed that the utilization of hospital service among patients with employment injury insurance and fund reimbursement provided by the local governmentwere higher than those without employment injury insurancea nd without fund reimbursement provided by the local government(all P<0.05). The utilization of hospital service of patients with problems in usual activities and those unable to perform usual activities were higher than those without any problems(P<0.05). The utilization hospital service of patients with VAS scores <60 was higher than those with VAS scores of 60-<75(P<0.05). CONCLUSION: The patients with pneumoconiosis have a relatively overall high level of utilization of hospital service. The employment injury insurance, fund reimbursement provided by the local government, VAS score, and status of physical health are important influencing factors of utilization of hospital service.