Inflammatory cells and cytokines production in chalazia

Purpose Aim of the present study was to localize the different types of inflammatory cells and cytokines in chalazion lesions to determine the sequence of events in cellular reaction. Methods Fifty four chalazia surgically removed by excision were fixed in Bouin’s solution and imbedded in paraffin. For immunohistochemical studies we used CD68, CD3, CD4, CD8, CD45RO, lactoferrin antibodies to detect respectively macrophages, T cells, T helper, T cytotoxic, mature activated T lymphocytes and neutrophils. For detection of cytokines we used IFN gamma and TNF alpha antibodies. The EnVision peroxidase detection system were used and the immmunoreactivity was visualized with diaminobenzidine. Results Large numbers of macrophages infiltrated the stroma around the alveoli and the glandular tissue of the chalazion lesions. Lower numbers of the neutrophils were found with similar distribution to macrophages. CD3(+) lymphocytes also accumulated in large numbers in the stroma, around the glands, and in the areas of granulomatous inflammation indicating an association with macrophages and neutrophils. Within the T-cell population, numerous CD8(+) cells, fewer CD4(+) cells, many CD45RO(+) cells were present. Positivity for IFN-gamma and TNF-alpha was showed in granulomatous areas and near vessels. Conclusion These cells play a significant role in the formation of the chalazion lesion. Neutrophils might be recruited into granulomatous lesions from the blood and may subsequently promote inflammatory cells accumulation both by direct cell to cell interactions and through the interaction of cytokines. The presence of IFN-gamma and TNF alpha suggests that these cytokines play a paracrine role in chalazion inflammatio

Eosinophilia-associated muscle disorders:an immunohistological study with tissue localisation of major basic protein in distinct clinicopathological forms

Aims: (a) To evaluate tissue eosinophil density, location of eosinophil cytotoxic products, histopathological muscle changes and inflammatory cell types in different eosinophilia-associated myopathies that are clinicopathologically heterogeneous. (b) To determine the immunohistological range of tissue eosinophil density in noneosinophilic inflammatory myopathies. Methods: Muscle biopsy specimens from seven patients with blood and/or tissue eosinophilia and clinicolaboratory myopathic signs (five chronic course myopathies, one subacute onset fasciitis/myositis, one acute myositis), and from 18 non-eosinophilic inflammatory myopathies, underwent routine staining, inflammatory infiltrate immunophenotyping, immunostaining for eosinophil major basic protein (MBP) and transmission electron microscopy examination. Eosinophil and total inflammatory cell counts were statistically analysed. Results: Histological examination showed occasional or no infiltrating eosinophils in all cases. MBP staining showed that tissue eosinophil density and percentages in eosinophilia-associated myopathies were significantly higher than in idiopathic myositides. Extracellular MBP diffusion, the hallmark of eosinophil cytotoxicity, was recurrent on sarcolemma and endothelium. Electron microscopy showed eosinophils close to sarcolemma, abundant mast cells, and capillary endothelial swelling. Immunostaining detected a higher mean eosinophil density in idiopathic myositides than previously assessed histologically. Conclusions: MBP immunohistology on skeletal muscle, previously performed only for acute eosinophilic polymyositis, suggests that eosinophil-mediated injury of muscle cells may occur in a wider spectrum of less aggressive eosinophilia-associated myopathies than previously thought. As conventional histology is likely to underestimate this leucocyte subset, MBP staining may be a useful tool in the analysis of tissue infiltration of eosinophils as a possible treatment target

Additional file 1: of IL-27 mediates HLA class I up-regulation, which can be inhibited by the IL-6 pathway, in HLA-deficient Small Cell Lung Cancer cells

IL-27 mediates HLA class I up-regulation, which can be inhibited by the IL-6 pathway, in HLA-deficient Small Cell Lung Cancer cells. Supplementary Figures and Table. (DOCX 2856 kb

Proteomic analysis uncovers common effects of IFN-\u3b3 and IL-27 on the HLA class I antigen presentation machinery in human cancer cells

IL-27, a member of the IL-12-family of cytokines, has shown anti-tumor activity in several pre-clinical models due to anti-proliferative, anti-angiogenic and immune-enhancing effects. On the other hand, IL-27 demonstrated immune regulatory activities and inhibition of auto-immunity in mouse models. Also, we reported that IL-27, similar to IFN-\u3b3, induces the expression of IL-18BP, IDO and PD-L1 immune regulatory molecules in human cancer cells. Here, a proteomic analysis reveals that IL-27 and IFN-\u3b3 display a broad overlap of functions on human ovarian cancer cells. Indeed, among 990 proteins modulated by either cytokine treatment in SKOV3 cells, 814 showed a concordant modulation by both cytokines, while a smaller number (176) were differentially modulated. The most up-regulated proteins were common to both IFN-\u3b3 and IL-27. In addition, functional analysis of IL-27-regulated protein networks highlighted pathways of interferon signaling and regulation, antigen presentation, protection from natural killer cell-mediated cytotoxicity, regulation of protein polyubiquitination and proteasome, aminoacid catabolism and regulation of viral protein levels.Importantly, we found that IL-27 induced HLA class I molecule expression in human cancer cells of different histotypes, including tumor cells showing very low expression. IL-27 failed only in a cancer cell line bearing a homozygous deletion in the B2M gene. Altogether, these data point out to a broad set of activities shared by IL-27 and IFN-\u3b3, which are dependent on the common activation of the STAT1 pathway. These data add further explanation to the anti-tumor activity of IL-27 and also to its dual role in immune regulation