Anti-F4/80 monoclonal antibody, clone CN9.2 [PerCP/Cy5.5®]

Background: Asthmatic chronic rhinosinusitis with nasal polyps (aCRSwNP) is a common disruptive eosinophilic disease without effective medical treatment. Therefore, we sought to identify gene expression changes, particularly those occurring early, in aCRSwNP. To highlight expression changes associated with eosinophilic epithelial inflammation, we further compared the changes in aCRSwNP with those in a second eosinophilic epithelial disease, atopic dermatitis (AD), which is also closely related to asthma. Methods/Principal Findings: Genome-wide mRNA levels measured by exon array in both nasosinus inflamed mucosa and adjacent polyp from 11 aCRSwNP patients were compared to those in nasosinus tissue from 17 normal or rhinitis subjects without polyps. Differential expression of selected genes was confirmed by qRT-PCR or immunoassay, and transcription changes common to AD were identified. Comparison of aCRSwNP inflamed mucosa and polyp to normal/rhinitis tissue identified 447 differentially transcribed genes at $2 fold-change and adjusted p-value, 0.05. These included increased transcription of chemokines localized to chromosome 17q11.2 (CCL13, CCL2, CCL8, and CCL11) that favor eosinophil and monocyte chemotaxis and chemokines (CCL18, CCL22, and CXCL13) that alternatively-activated monocyte-derived cells have been shown to produce. Additional transcription changes likely associated with Th2-like eosinophilic inflammation were prominent and included increased IL1RL1 (IL33 receptor) and EMR1&3 and decreased CRISP2&3. A down-regulated PDGFB-centric network involving several smooth muscle-associated genes was also implicated. Genes at 17q11.2, genes associated with alternative activation or smooth muscle, and the IL1RL1 gene were also differentially transcribed in AD. Conclusions/Significance: Our data implicate several genes or gene sets in aCRSwNP and eosinophilic epithelial inflammation, some that likely act in the earlier stages of inflammation. The identified gene expression changes provide additional diagnostic and therapeutic targets for aCRSwNP and other eosinophilic epithelial diseases.

Chronic low-grade inflammation in obesity is characterized by macrophage accumulation in white adipose tissue (WAT) and abnormal cytokine production. We tested the hypothesis that grape-seed procyanidin extract (PE), with known anti-inflammatory and antioxidant effects, would improve local and systemic inflammation in diet-induced obesity rats. First, we analyzed the preventive effects of procyanidins (30 mg/kg per day) on rats fed a 60% kcal fat diet for 19 weeks. Second, we induced cafeteria diet obesity for 13 weeks to investigate the corrective effects of two PE doses (25 and 50 mg/kg per day) for 10 and 30 days. In the preventive model, PE group had reduced not only body weight but also plasmatic systemic markers of inflammation tumor necrosis factor-alpha (TNF-alpha) and C-reactive protein (CRP). The PE preventive treatment significantly showed an increased adiponectin expression and decreased INF-alpha, interleukin-6 and CRP expression in mesenteric WAT and muscle TNF-alpha. A reduced NF-kappa B activity in liver is also observed which can be related to low expression rates of hepatic inflammatory markers found in PE group. Finally, PE dietary supplementation is linked to a reduced expression of Emr1 (specific marker of macrophage F4/80), which suggests a reduced macrophage infiltration of WAT. In the corrective model, however, only the high dose of PE reduced CRP plasma levels in the short treatment without changes in plasmatic INF-alpha. In conclusion, orally ingested PE helps preventing imbalanced obesity cytokine pattern, but its corrective effects need to be further investigated. The dietary regular intake of food or drinks containing procyanidins might help prevent low-grade inflammatory-related diseases. (C) 2011 Elsevier Inc. All rights reserved.