Radiah C. Minor

Scavenger receptor class-A is a novel cell surface receptor for double-stranded RNA

Double‐stranded RNA (dsRNA) is a potent signal to the host immune system for the presence of an ongoing viral infection. The presence of dsRNA, intracellularly or extracellularly, leads to the induction of innate inflammatory cytokines in many cell types including epithelial cells. However, the cell surface receptor for recognition of extracellular dsRNA is not yet determined. Here, we report that extracellular dsRNA is recognized and internalized by scavenger receptor class‐A (SR‐A). Treatment of human epithelial cells with specific antagonists of SR‐A or with an anti‐SRA antibody significantly inhibited dsRNA induction of tumor necrosis factor (TNF)‐α, interleukin (IL)‐6, IL‐8, and regulated on activation normal T‐cell expressed and secreted (RANTES). Furthermore, intranasal dsRNA treatment of SR‐A‐deficient (SR‐A−/−) mice showed a significant decrease in the expression of inflammatory cytokines and a corresponding decrease in the accumulation of polymorphonuclear leukocytes (PMNs) in lungs. These data provide direct evidence that SR‐A is a novel cell surface receptor for dsRNA, and therefore, SR‐Amay play a role in antiviral immune responses.— Limmon, G. V., Arredouani, M., McCann, K. L., Corn Minor, R. A., Kobzik, L., Imani, L. Scavenger receptor class‐A is a novel cell surface receptor for double‐stranded RNA. FASEB J. 22, 159–167 (2008)

Double-stranded RNA-activated protein kinase regulates early innate immune responses during respiratory syncytial virus infection.

Respiratory syncytial virus (RSV) is the most common cause of childhood viral bronchiolitis and lung injury. Inflammatory responses significantly contribute to lung pathologies during RSV infections and bronchiolitis but the exact mechanisms have not been completely defined. The double-stranded RNA-activated protein kinase (PKR) functions to inhibit viral replication and participates in several signaling pathways associated with innate inflammatory immune responses. Using a functionally defective PKR (PKR(-/-)) mouse model, we investigated the role of this kinase in early events of RSV-induced inflammation. Our data showed that bronchoalveolar lavage (BAL) fluid from infected PKR(-/-) mice had significantly lower levels of several innate inflammatory cytokines and chemokines. Histological examinations revealed that there was less lung injury in infected PKR(-/-) mice as compared to the wild type. A genome-wide analysis showed that several early antiviral and immune regulatory genes were affected by PKR activation. These data suggest that PKR is a signaling molecule for immune responses during RSV infections.

Effect of Rosehip (Rosa canina) Extracts on Human Brain Tumor Cell Proliferation and Apoptosis

Rosehips are blossoms from the wild rose (Rosa canina) and are commonly used as an herbal remedy. Previous reports have shown that extracts made from rosehip plants are able to reduce cell proliferation of cancer cells. In this study, we investigated the efficacy of rosehip extracts in preventing cell proliferation of three human glioblastoma cell lines A-172, U-251 MG and U-1242 MG cell lines. Each of the glioblastoma cell lines treated with rosehip extracts (1 mg/mL-25 ng/mL) demonstrated a significant decrease in cell proliferation. The rosehip extract-mediated decrease in cell proliferation was equal to or better than the decrease of cell proliferation observed when inhibitors of the MAPK (U0126, 10 μM) or AKT (LY294002, 20 μM) signaling pathways were utilized. Additionally, pretreatment of the these cell lines with Rosehip extracts (1 mg/mL-25 ng/mL) selectively decreased AKT, MAPK, and p70S6K phosphorylation suggesting these extracts prevent glioblastoma multiforme cell proliferation by blocking both the MAPK and AKT signaling mechanisms. Results from colorimetric cell death assays, cell cycle analysis by flow cytometry, as well as western blot studies demonstrate that rosehip extracts inhibit cell proliferation but do not promote apoptosis. Moreover, rosehip extracts were able to increase the efficacy of Temozolomide, a chemotherapeutic agent used to treat patients with glioblastomas. Surprisingly, rosehip extracts demonstrated a greater inhibition of cell proliferation than in combination with Temozolomide (100 μM) or Temozolomide as a single agent. Taken together these data suggest that rosehip extracts are capable of decreasing glioblastoma cell proliferation without promoting apoptosis and demonstrate a greater cell proliferation inhibitory effect than Temozolomide. More importantly, rosehip extracts may serve as an alternative or compliment to current chemotherapeutic regimens for glioblastomas.

Inclusion of Oat in Feeding Can Increase the Potential Probiotic Bifidobacteria in Sow Milk

Simple Summary In this study we isolated and characterized potential probiotic bifidobacteria from sow milk. The bifidobacterial population in milk has been attributed to the existence of prebiotic oat in feeding systems. Since breast feeding protects the newborns against several infectious diseases, milk from sows fed with oat could improve the health of piglets. Abstract The objectives of this study were to (i) investigate the impact of feeding oat on the population of bifidobacteria and (ii) evaluate their probiotic potential. In this study, we investigated the effects of supplementing sows’ gestation and lactation feed with 15% oat (prebiotic source) on the levels of probiotic population in milk. We found that dietary inclusion of oat during lactation and gestation resulted in increased levels of bifidobacteria compared to lactobacilli in sow milk. Furthermore bifidobacteria within the sow milk samples were further evaluated for probiotic potential based on aggregating properties, and acid- and bile-tolerance after exposure to hydrochloric acid (pH 2.5) and bile salts (0%, 0.25%, 0.50%, 1.0% and 2.0%). All isolates survived under the condition of low pH and bile 2.0%. Autoaggregation ability ranged from 17.5% to 73%. These isolates also showed antimicrobial activity against E. coli O157:H7. Together our results suggest that inclusion of oat in feeding systems could have the potential to improve the intestinal health of piglets by increasing the population of bifidobacteria.