Staphylococcus aureus enterotoxins induce IL-8 secretion by human nasal epithelial cells

BACKGROUND: Staphylococcus aureus produces a set of proteins which act both as superantigens and toxins. Although their mode of action as superantigens is well understood, little is known about their effects on airway epithelial cells. METHODS: To investigate this problem, primary nasal epithelial cells derived from normal and asthmatic subjects were stimulated with staphylococcal enterotoxin A and B (SEA and SEB) and secreted (supernatants) and cell-associated (cell lysates) IL-8, TNF-α, RANTES and eotaxin were determined by specific ELISAs. RESULTS: Non-toxic concentrations of SEA and SEB (0.01 μg/ml and 1.0 μg/ml) induced IL-8 secretion after 24 h of culture. Pre-treatment of the cells with IFN-γ (50 IU/ml) resulted in a further increase of IL-8 secretion. In cells from healthy donors pretreated with IFN-γ, SEA at 1.0 μg/ml induced release of 1009 pg/ml IL-8 (733.0–1216 pg/ml, median (range)) while in cells from asthmatic donors the same treatment induced significantly higher IL-8 secretion – 1550 pg/ml (1168.0–2000.0 pg/ml p = 0.04). Normal cells pre-treated with IFN-γ and then cultured with SEB at 1.0 μg/ml released 904.6 pg/ml IL-8 (666.5–1169.0 pg/ml). Cells from asthmatics treated in the same way produced significantly higher amounts of IL-8 – 1665.0 pg/ml (1168.0–2000.0 pg/ml, p = 0.01). Blocking antibodies to MHC class II molecules added to cultures stimulated with SEA and SEB, reduced IL-8 secretion by about 40% in IFN-γ unstimulated cultures and 75% in IFN-γ stimulated cultures. No secretion of TNF-α, RANTES and eotaxin was noted. CONCLUSION: Staphylococcal enterotoxins may have a role in the pathogenesis of asthma

Different Types of Cell Death Induced by Enterotoxins

The infection of bacterial organisms generally causes cell death to facilitate microbial invasion and immune escape, both of which are involved in the pathogenesis of infectious diseases. In addition to the intercellular infectious processes, pathogen-produced/secreted enterotoxins (mostly exotoxins) are the major weapons that kill host cells and cause diseases by inducing different types of cell death, particularly apoptosis and necrosis. Blocking these enterotoxins with synthetic drugs and vaccines is important for treating patients with infectious diseases. Studies of enterotoxin-induced apoptotic and necrotic mechanisms have helped us to create efficient strategies to use against these well-characterized cytopathic toxins. In this article, we review the induction of the different types of cell death from various bacterial enterotoxins, such as staphylococcal enterotoxin B, staphylococcal alpha-toxin, Panton-Valentine leukocidin, alpha-hemolysin of Escherichia coli, Shiga toxins, cytotoxic necrotizing factor 1, heat-labile enterotoxins, and the cholera toxin, Vibrio cholerae. In addition, necrosis caused by pore-forming toxins, apoptotic signaling through cross-talk pathways involving mitochondrial damage, endoplasmic reticulum stress, and lysosomal injury is discussed

Neurobehavioral outcome and subthalamic deep brain stimulation in Parkinson\u27s disease

Subthalamic deep brain stimulation (STN DBS) is known to improve motor functioning in Parkinson\u27s Disease (PD), but the neurobehavioral impact is less clear. This study examined neurobehavioral outcome of bilateral STN DBS in advanced PD. Study participants were assigned to either a Surgical Group (n=19) or a waitlist Control Group (n=16) and assessed twice. Between assessments, there was a two month interval during which the Surgical Group had STN DBS surgery, while the Control Group had no surgery. In comparison to the Control Group, the Surgical Group showed significant decline in executive functioning, verbal delayed memory, verbal working memory, and verbal fluency. Nevertheless, the Surgical Group also reported significantly improved health and quality of life in several domains including vitality, mental health, general health, and social functioning. In summary, this study revealed that despite declines on several cognitive measures, participants who underwent STN DBS also reported improved quality of life

Congenital peribronchial myofibroblastic tumor: Case report and review of literature

Congenital peribronchial myofibroblastic tumor (CPMT) is a rare entity recognized in the WHO classification of pulmonary neoplasms. According to available literature, it is a benign tumor with a high mortality rate exceeding 50%. It is partially attributed to polyhydramnios, hydrops, prematurity, respiratory distress or adverse surgical outcomes due to intraoperative bleeding. Herein we present a case of congenital peribronchial myofibroblastic tumor in a premature male infant who was born at 31 weeks gestation due to polyhydramnios and premature rupture of membranes. Soon after birth, he required intubation due to worsening respiratory distress. Imaging demonstrated a large right chest mass causing mediastinal shift. Surgical intervention was attempted, which was challenging due to intraoperative bleeding and tumor retraction. The patient expired soon after the surgery. Hence, in this report we would like to share our experience with this difficult diagnosis and treatment of this rare tumor

An Oligomeric Sulfated Hyaluronan and Silk-Elastinlike Polymer Combination Protects against Murine Radiation Induced Proctitis

Semisynthetic glycosaminoglycan ethers (SAGEs) are short, sulfated hyaluronans which combine the natural properties of hyaluronan with chemical sulfation. In a murine model, SAGEs provide protection against radiation induced proctitis (RIP), a side effect of lower abdominal radiotherapy for cancer. The anti-inflammatory effects of SAGE have been studied in inflammatory diseases at mucosal barrier sites; however, few mechanisms have been uncovered necessitating high throughput methods. SAGEs were combined with silk-elastinlike polymers (SELPs) to enhance rectal accumulation in mice. After high radiation exposure to the lower abdominal area, mice were followed for 3 days or until they met humane endpoints, before evaluation of behavioral pain responses and histological assessment of rectal inflammation. RNA sequencing was conducted on tissues from the 3-day cohort to determine molecular mechanisms of SAGE–SELP. After 3 days, mice receiving the SAGE–SELP combination yielded significantly lowered pain responses and amelioration of radiation-induced rectal inflammation. Mice receiving the drug–polymer combination survived 60% longer than other irradiated mice, with a fraction exhibiting long term survival. Sequencing reveals varied regulation of toll like receptors, antioxidant activities, T-cell signaling, and pathways associated with pain. This investigation elucidates several molecular mechanisms of SAGEs and exhibits promising measures for prevention of RIP

Preparation and Characterization of Self-Assembled Poly(l-Lactide) on the Surface of β-Tricalcium Diphosphate(V) for Bone Tissue Theranostics

This work was aimed to obtain and characterize the well-defined biocomposites based on β-tricalcium diphosphate(V) (β-TCP) co-doped with Ce3+ and Pr3+ ions modified by poly(l-lactide) (PLLA) with precise tailored chain length and different phosphate to polymer ratio. The composites as well as β-tricalcium diphosphate(V) were spectroscopically characterized using emission spectroscopy and luminescence kinetics. Morphological and structural properties were studied using X-Ray Diffraction (XRD) and Scanning Electron Microscopy (SEM). The self-assembled poly(l-lactide) in a shape of rose flower has been successfully polymerized on the surface of the β-tricalcium diphosphate(V) nanocrystals. The studied materials were evaluated in vitro including cytotoxicity (MTT assay) and hemolysis tests. The obtained results suggested that the studied materials may find potential application in tissue engineering