The transcription factor MafB is expressed by monocytes and macrophages. Efferocytosis (apoptotic cell uptake) by macrophages is important for inhibiting the development of autoimmune diseases, and is greatly reduced in Mafb-deficient macrophages. Here, we show the expression of the first protein in the classical complement pathway C1q is important for mediating efferocytosis and is reduced in Mafb-deficient macrophages. The efferocytosis defect in Mafb-deficient macrophages can be rescued by adding serum from wild-type mice, but not by adding serum from C1q-deficient mice. By hemolysis assay we also show that activation of the classical complement pathway is decreased in Mafb-deficient mice. In addition, MafB overexpression induces C1q-dependent gene expression and signals that induce C1q genes are less effective in the absence of MafB. We also show that Mafb-deficiency can increase glomerular autoimmunity, including anti-nuclear antibody deposition. These results show that MafB is an important regulator of C1q.
Background In recent years, rapid increase of elderly population has become a major social problem in developed countries. They tend to receive an increasing number of prescibed drugs due to multiple illnesses, which might include inappropriate medications, in turn leading to health hazards and rising healthcare cost. Objective To evaluate the current status of potentially inappropriate medications prescribed for elderly outpatients and filled by dispensing pharmacies using the recent Japanese Guidelines, and to determine factors that are related to prescribing potentially inappropriate medications. Setting A crosssectional study of older patients (≥ 75 years) who visited dispensing pharmacies in the Ibaraki Prefecture, Japan. Method We identified patients prescribed potentially inappropriate medications using the "List of Medications that Require Particularly Careful Administration" in the Guidelines (Guideline List). We explored patient's factors related to polypharmacy (≥ 5 medications) and prescription of inappropriate medications through multivariate analysis, and a cutoff value for predicting potentially inappropriate medications through receiver operating characteristic curve analysis. Main outcome measure Prevalence of polypharmacy and potentially inappropriate medications, and patient's factors associated with them. Results Of 8080 patients (39,252 medications) who visited pharmacies during the study period, 43.1% (3481) were prescribed ≥ 5 medications. In total, 2157 patients (26.7%) were prescribed at least one potentially inappropriate medication. The most prescribed inappropriate medication class was (benzodiazepine) sedatives and hypnotics. Potentially inappropriate medications were 7.11 times (95% CI 6.29-8.03) and 1.51 times (1.34-1.71) more likely to be prescribed for patients with ≥ 5 medications and those prescribed by multiple physicians, respectively. A cutoff value for potentially inappropriate medications was found to be five for the total number of medications and four for the number of chronic medications with a systemic effect. Conclusion Prescription of potentially inappropriate medications was increased among patients with ≥ 5 medications and those chronically prescribed ≥ 4 medications with a systemic effect. The Guideline List should be actively used to screen such patients, and to carefully examine prescriptions. Particular care should be exercised when patients are visiting multiple physicians.
MafB, a transcription factor expressed selectively in macrophages, has important roles in some macrophage‐related diseases, especially in atherosclerosis. In this study, we investigated the mechanism by which hematopoietic‐specific MafB deficiency induces the development of obesity. Wild‐type and hematopoietic cell‐specific Mafb ‐deficient mice were fed a high‐fat diet for 10 weeks. The Mafb ‐deficient mice exhibited higher body weights and faster rates of body weight increase than control mice. The Mafb ‐deficient mice also had a higher percentage of body fat than the wild‐type mice, due to increased adipocyte size and serum cholesterol levels. Reverse transcription‐ PCR analysis showed a reduction in apoptosis inhibitor of macrophage ( AIM ) in Mafb ‐deficient adipose tissue. AIM is known as an inhibitor of lipogenesis in adipocytes and is expressed in adipose tissue macrophages. Collectively, our data suggest that Mafb deficiency in hematopoietic cells accelerates the development of obesity.
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