Increased concentration of soluble leukocyte-associated immunoglobulin-like receptor in sera from patients with blistering diseases: possible pathophysiological implications?

Background: Autoimmune blistering diseases (AIBD), are a heterogeneous group. Despite their pathogenesis is not completely understood, autoantibodies against directed adhesion molecules of the skin and adjacent mucous membranes could play a key role. The leukocyte-associated-Ig-like-receptor (LAIR) family is a small group of immunoreceptor-tyrosine-based-inhibition-motif-containing inhibitory receptors, recognizing collagens.

Homotypic and Heterotypic Activation of the Notch Pathway in Multiple Myeloma-Enhanced Angiogenesis: A Novel Therapeutic Target?

Interactions of multiple myeloma (MM) cells with endothelial cells (ECs) enhance angiogenesis and MM progression. Here, we investigated the role of Notch signaling in the cross talk between ECs and MM cells enabling angiogenesis. MMECs showed higher expression of Jagged1/2 ligands, of activated Notch1/2 receptors, and of Hes1/Hey1 Notch target genes than ECs from monoclonal gammopathy of undetermined significance patients, suggesting that homotypic activation of Notch pathway occurs in MM.

Bone marrow fibroblasts overexpress miR-27b and miR-214 in step with multiple myeloma progression, dependent on tumour cell-derived exosomes.

Aberrant microRNA (miR) expression has an important role in tumour progression, but its involvement in bone marrow fibroblasts of multiple myeloma patients remains undefined. We demonstrate that a specific miR profile in bone marrow fibroblasts parallels the transition from monoclonal gammopathy of undetermined significance (MGUS) to myeloma. Overexpression of miR-27b-3p and miR-214-3p triggers proliferation and apoptosis resistance in myeloma fibroblasts via the FBXW7 and PTEN/AKT/GSK3 pathways, respectively.

Definition of a new cut-off for the anti-phospholipase A2 receptor (PLA2R) autoantibody immunoassay in patients affected by idiopathic membranous nephropathy.

Autoantibodies against phospholipase A2 receptor (PLA2R) are a sensitive and specific marker for idiopathic membranous nephropathy (IMN). The aim of our study was to redefine the cut-off value for the measurement of anti-PLA2R autoantibody levels by an automated enzyme immunoassay, in a large single-center cohort of Italian IMN patients at the time of diagnosis. Sixty-seven consecutive incident patients, with biopsy-proven IMN, were recruited.

IL-6/IL-10 Ratio as A Prognostic and Predictive Marker of the Severity of Inherited Epidermolysis Bullosa.

Background: Recent studies have shown that cytokines have an important role in the pathogenesis of inflammatory diseases and can be used as prognostic markers.

Objective: To evaluate the IL-6/IL-10 ratio in patients with Inherited Epidermolysis Bullosa (EB) as a prognostic marker.

Methods: Serum levels of IL-6 and IL-10 were measured in 13 patients with recessive dystrophic EB (RDEB) as well as 10 with EB Simplex (EBS), and in 18 healthy subjects.

Microenvironment drug resistance in multiple myeloma: emerging new players.

Multiple myeloma (MM) drug resistance (DR) is a multistep transformation process based on a powerful interplay between bone marrow stromal cells and MM cells that allows the latter to escape anti-myeloma therapies. Here we present an overview of the role of the bone marrow microenvironment in both soluble factors-mediated drug resistance (SFM-DR) and cell adhesion-mediated drug resistance (CAM-DR), focusing on the role of new players, namely miRNAs, exosomes and cancer-associated fibroblasts.

Myeloma cells act as tolerogenic antigen-presenting cells and induce regulatory T cells in vitro.

Regulatory T cells (Tregs) are essential for maintenance of self-tolerance; however, tumor cells can exploit the tolerance to escape the immune system. We investigated the Tregs frequency in patients with multiple myeloma (MM) and in those with monoclonal gammopathy of undetermined significance (MGUS), and found that CD4(+) FoxP3(+) and CD8(+) FoxP3(+) Tregs were significantly increased in patients with MM and correlated with the active phase. Both Tregs subsets were expanded in cocultures of CD3(+) lymphocytes and fresh CD138(+) MM plasma cells or RPMI8226 and U266 cell lines and functioned as natural (n) and inducible (i) Tregs insofar as they inhibited the proliferation of stimulated CD3 lymphocytes via contact-dependent and contact-independent pathways.

Survivin promoter -31G/C polymorphism in oral cancer cell lines.

Survivin (SVV) is a protein that belongs to the inhibitor of apoptosis proteins (IAP) family and is involved in the G2/M phase progression of the cell cycle as a spindle‑associated molecule. The biological features of this protein are well documented and its activity appears to be involved in mitochondria-dependent and -independent antiapoptotic pathways. Overexpression of SVV at the transcriptional and translational level has been associated with cancer, a multifactorial disorder in which the occurrence of a -31G to C polymorphism in the promoter region may significantly contribute to the development of this pathology.

Increase in interleukin-8 production from circulating neutrophils upon antibiotic therapy in cystic fibrosis patients.

Background: It is not known whether antibiotic therapy for lung disease in cystic fibrosis (CF) has an influence on circulating polymorphonuclear neutrophil (PMN) function and apoptosis.

Patients And Methods: Blood PMNs were obtained from 14 CF patients before and after antibiotic treatment for an acute exacerbation, and from 10 healthy controls. PMNs were evaluated for production of reactive oxygen species (ROS) by spectrophotometry, of cytokines in the conditioned medium by ELISA, and apoptotic response by cytofluorimetry.

Molecular pathways in cancer-related inflammation.

Accumulating evidence shows that chronic inflammation is associated to increased risk of cancer. An inflammatory component is present also in the microenvironment of tumours epidemiologically unrelated to inflammation. Extensive investigations over the past decade have uncovered many of the important mechanistic pathways underlying cancer-related inflammation.

Streptococcus pneumoniae modulates the respiratory burst response in human neutrophils.

The gram-positive pathogen Streptococcus pneumoniae is the most common cause of community-acquired pneumonia and is responsible for high morbidity and mortality worldwide. A major feature of pneumococcal pneumonia is an abundant neutrophil infiltration. In this work we observed that the R6 nonencapsulated S.

Exogenous factors in the immunotoxicity of oral PMN.

Current evidence indicates that periodontal disease is frequently due to inappropriate levels of gingival granulocyte functions. Reason of this failure may be the toxic effects of a number of local or systemic exogenous factors, capable of spreading through the gingival crevice environment, and strongly conditioning the granulocyte activities. The wide list includes bacteria and granulotoxic products, hedonistic drugs (mainly tobacco), and chemotherapeutic agents (especially antimicrobials used for preventing or reducing the accumulation of dental plaque).

Neutrophil recruitment and airway epithelial cell involvement in chronic cystic fibrosis lung disease.

The pathological hallmark of cystic fibrosis (CF) chronic inflammatory response is the massive neutrophil influx into the airways. This dysregulated neutrophil emigration may be caused by the abnormal secretion of chemoattractants by respiratory epithelial cells and polarised lymphocyte T-helper response. Neutrophils from CF patients have a different response to inflammatory mediators than neutrophils from normal subjects, indicating that they are primed in vivo before entering the CF airways.

In vitro effects of polyamines on polymorphonuclear cell apoptosis and implications in the pathogenesis of periodontal disease.

Apoptosis provides a mechanism for clearance of unwanted cells in a variety of situations in which programmed or physiological cell death occurs; but the premature death of defensive cells could promote infection, inflammation and concomitant diseases. Polymorphonuclear cells (PMN) of gingival sulcus play an important role in host defense against periodontal tissue-invading bacteria, but their phagocytic activity is conditioned by several virulence factors released by oral pathogens. Polyamines derived from oral bacteria frequently occur at concentrations approaching 1 mM in gingival fluid at diseased periodontal sites.