Ubiquitin-Specific Protease 2 Modulates the Lipopolysaccharide-Elicited Expression of Proinflammatory Cytokines in Macrophage-like HL-60 Cells

We investigated the regulatory roles of USP2 in mRNA accumulation of proinflammatory cytokines in macrophage-like cells after stimulation with a toll-like receptor (TLR) 4 ligand, lipopolysaccharide (LPS). Human macrophage-like HL-60 cells, mouse macrophage-like J774.1 cells, and mouse peritoneal macrophages demonstrated negative feedback to USP2 mRNA levels after LPS stimulation, suggesting that USP2 plays a significant role in LPS-stimulated macrophages. USP2 knockdown (KD) by short hairpin RNA in HL-60 cells promoted the accumulation of transcripts for 25 of 104 cytokines after LPS stimulation. In contrast, limited induction of cytokines was observed in cells forcibly expressing the longer splice variant of USP2 (USP2A), or in peritoneal macrophages isolated from Usp2a transgenic mice. An ubiquitin isopeptidase-deficient USP2A mutant failed to suppress LPS-induced cytokine expression, suggesting that protein ubiquitination contributes to USP2-mediated cytokine repression. Although USP2 deficiency did not accelerate TNF receptor-associated factor (TRAF) 6-nuclear factor-κB (NF-κB) signaling, it increased the DNA binding ratio of the octamer binding transcription factor (Oct)-1 to Oct-2 in TNF, CXCL8, CCL4, and IL6 promoters. USP2 decreased nuclear Oct-2 protein levels in addition to decreasing the polyubiquitination of Oct-1. In summary, USP2 modulates proinflammatory cytokine induction, possibly through modification of Oct proteins, in macrophages following TLR4 activation

Caregiver Burden for Impaired Elderly Japanese with Prevalent Stroke and Dementia under Long-Term Care Insurance System

Background: Limited data are available on caregiver burden for stroke and dementia patients. We examined the associations of prevalent stroke and dementia with family caregiver burden in Japanese general populations. Methods: A total of 916 Japanese home caregivers, whose family members were covered by long-term care insurance, responded to the caregiver burden questionnaire. The questionnaire included the caregiver\u27s age, sex and employment status, the patient-caregiver relationship, the patient\u27s history of stroke, symptoms of dementia, care levels under long-term care insurance and the Zarit Caregiver Burden Interview. Results: The mean total score from the Zarit Caregiver Burden Interview was 12% higher in patients with stroke than in those without (p = 0.02) and 40% higher in those with dementia than in those without (p < 0.001). Compared with nonstroke patients without dementia, the mean total score was 21% higher in stroke patients without dementia (p = 0.01), 49% higher in nonstroke patients with dementia (p < 0.001) and 55% higher in stroke patients with dementia (p < 0.001). After adjustment for the caregiver\u27s age, sex and employment status, the patient-caregiver relationship, and the patient\u27s care level and community, the higher scores remained statistically significant for nonstroke patients with dementia and for stroke patients with dementia but not for stroke patients without dementia. Conclusions: Prevalent stroke and, more strongly, dementia were associated with increased family caregiver burden. Among patients with dementia, the presence of stroke did not enhance caregiver burden further

Brazilian propolis extract increases leptin expression in mouse adipocytes

We investigated the anti-obesity effects of Brazilian green propolis ethanol extract using a mouse model of obesity. Repeated intraperitoneal injection of propolis (100 mg/kg twice a week) caused feeding suppression in C57BL/6 mice, whereas this treatment had negligible effects on C57BL/6 ob/ob mice. Since C57BL/6 ob/ob mice have a missense mutation in the Lep gene, leptin is likely to contribute to the propolis-induced feeding suppression. We found that propolis treatment indeed clearly increased leptin mRNA production in the visceral adipose tissues. Moreover, propolis extract directly elevated leptin expression in differentiated 3T3-L1 adipocytes. Artepillin C, an important organic compound found in Brazilian green propolis, failed to induce leptin mRNA in 3T3-L1 cells. Compounds other than artepillin C in Brazilian propolis must thus cause leptin induction in adipocytes, possibly resulting in the suppression of feeding and obesity