Interleukin-9 Overexpression and Th9 Polarization Characterize the Inflamed Gut, the Synovial Tissue, and the Peripheral Blood of Patients With Psoriatic Arthritis

Objective To investigate the expression and tissue distribution of Th9-related cytokines in patients with psoriatic arthritis (PsA). Methods Quantitative gene expression analysis of Th1, Th17, and Th9 cytokines was performed in intestinal biopsy samples obtained from patients with PsA, HLA-B27-positive patients with ankylosing spondylitis (AS), patients with Crohn's disease (CD), and healthy controls. Expression and tissue distribution of interleukin-23 (IL-23), IL-17, IL-22, IL-9, and IL-9 receptor (IL-9R) were evaluated by immunohistochemistry and confocal microscopy. Flow cytometry was used to study the frequency of Th9 cells among peripheral blood, lamina propria, and synovial fluid mon…

Familial hypobetalipoproteinemia due to apolipoprotein B R463W mutation causes intestinal fat accumulation and low postprandial lipemia

Abstract Objective Familial hypobetalipoproteinemia (FHBL) is characterized by inherited low plasma levels of apolipoprotein B (apoB)-containing lipoproteins. In this paper we investigated whether the already described APOB R463W missense mutation, a FHBL mutation able to impair the activity of microsomal triglyceride transfer protein (MTP), may cause intestinal fat accumulation and reduced postprandial lipemia. Methods Four out of five probands harboring APOB R463W mutation were compared with six healthy controls and six patients with celiac disease (CD). An oral fat load supplemented with retinyl palmitate (RP) was administered and a gastro-duodenal endoscopy with biopsy was performed. Re…

Interleukin (IL)-22 receptor 1 is over-expressed in primary Sjogren's syndrome and Sjögren-associated non-Hodgkin lymphomas and is regulated by IL-18.

Summary The aim of this study was to elucidate more clearly the role of interleukin (IL)-18 in modulating the IL-22 pathway in primary Sjögren's syndrome (pSS) patients and in pSS-associated lymphomas. Minor salivary glands (MSGs) from patients with pSS and non-specific chronic sialoadenitis (nSCS), parotid glands biopsies from non-Hodgkin lymphomas (NHL) developed in pSS patients, were evaluated for IL-18, IL-22, IL-22 receptor 1 (IL-22R1), IL-22 binding protein (IL-22BP) and signal transducer and activator of transcription-3 (STAT-3) expression. MSGs IL-22R1-expressing cells were characterized by confocal microscopy and flow cytometry in pSS, nSCS and healthy controls. The effect of recom…

Ectopic expression of CXCL13, BAFF, APRIL and LT-ß is associated with artery tertiary lymphoid organs in giant cell arteritis

ObjectivesTo investigate whether artery tertiary lymphoid organs (ATLOs) are present in giant cell arteritis (GCA) and that their formation is associated with the ectopic expression of constitutive lymphoid tissue-homing chemokines.MethodsReverse transcriptase PCR, immunohistochemical and immunofluorescence analysis were used to determine the presence of ectopic ATLOs in GCA and the expression of chemokines/chemokine receptors and cytokines involved in lymphoneogenesis in the temporal artery samples obtained from 50 patients with GCA and 30 controls. The presence of lymphatic conduits, of follicular dendritic cells (FDCs) precursors and lymphoid tissue inducer cells was also investigated. F…

Difference in the expression of IL-9 and IL-17 correlates with different histological pattern of vascular wall injury in giant cell arteritis

OBJECTIVE: GCA is a large- and medium-vessel arteritis characterized by a range of histological patterns of vascular wall injury. The aim of this study was to immunologically characterize the various histological patterns of GCA. METHODS: Thirty-five consecutive patients with biopsy-proven GCA and 15 normal controls were studied. IL-8, IL-9, IL-9R, IL-17, IL-4, TGF-β and thymic stromal lymphopoietin expression was evaluated by RT-PCR and immunohistochemistry on artery biopsy specimens. Confocal microscopy was used to characterize the phenotypes of IL-9-producing and IL-9R-expressing cells. Five additional patients who had received prednisone when the temporal artery biopsy was performed wer…

Rituximab modulates IL-17 expression in the salivary glands of patients with primary Sjögren's syndrome.

OBJECTIVE: The aim of this study was to evaluate the role of rituximab (RTX) in modulating the expression of the IL-17/IL-23 pathway in the salivary glands (SGs) of patients with primary SS (pSS). METHODS: Consecutive SG biopsies were obtained from 15 patients with pSS before and after 1 year of RTX therapy. The SG expression of IL-17, IL-23p19 and p-STAT3 was evaluated by immunohistochemistry at baseline and after RTX therapy. The role of mast cells in pSS patients in modulating the Th17 response and the immunologic effect of RTX on mast cells were also studied in in vitro experiments. RESULTS: IL-17 was overexpressed in the SGs of patients with pSS mainly by infiltrating T cells and mast …

Metabolomic analysis of plasma from Alzheimer disease patients

Alzheimer Disease is a degenerative disease characterized by progressive impairment of cognitive function. The main feature of AD the generation of an abnormal peptide, beta amyloid 42 (Ab42) from Amyloid Precursor Protein (APP). Ab42 is the main constituent of neurotangles and amyloid plaques, microscopic lesions found in AD patients brain. Ab42 triggers an inflammatory response that is responsible for most of the observed tissue damage. The diagnosis of AD is a complex task, mostly based on imaging techniques and clinical evaluation of the patient’s neurological and cognitive functions. The search for plasma biomarkers able to detect early mild cognitive impairment is one of the recent at…

In vitro antitumor effects of the cold-water extracts of Mediterranean species of genus Pleurotus (higher Basidiomycetes) on human colon cancer cells

The aim of this study was to evaluate whether the cold-water extracts of Pleurotus eryngii var. ferulae (CWE-Pef) and Pleurotus nebrodensis (CWE-Pn), 2 of the most prized wild and cultivated edible mushrooms, can affect the tumor phenotype of human colon cancer HCT116 cells. Our results showed that treatment with CWE- Pef and CWE-Pn resulted in a significant inhibition of the viability of HCT116 cells and promoted apoptosis, as also demonstrated by the increase of Bax-to-Bcl-2 messenger RNA ratio. Moreover, we observed that both extracts were able to inhibit cell migration and to affect homotypic and heterotypic cell-cell adhesion. It also was found that treatment with CWE-Pef and CWE-Pn ne…

In vitro antitumor effects of the cold-water extracts of Pleurotus eryngii var ferulae and Pleurotus nebrodensis on human colon cancer cells

For centuries, mushrooms have been used as folk medicines especially in Asian countries where their medicinal properties are well known. On the basis of numerous experimental evidences collected in the last decades, the immunomodulatory and anti-neoplastic properties of substances extracted from various species belonging to genera of edible mushrooms [Agaricus L., Auricularia Bull. ex Juss., Ganoderma P. Karst., Grifola Gray, Lentinus Fr., Schizophyllum Fr., Tremella Dill ex L., etc.] are extensively recognized also at scientific levels. Several works have demonstrate that anti-cancer property of these molecules is due to their ability to enhance immune system activity and/or to act directl…

Evidence that autophagy, but not the unfolded protein response, regulates the expression of IL-23 in the gut of patients with ankylosing spondylitis and subclinical gut inflammation

OBJECTIVES: Interleukin (IL)-23 has been implicated in the pathogenesis of ankylosing spondylitis (AS). The aim of the study was to clarify the mechanisms underlying the increased IL-23 expression in the gut of AS patients. METHODS: Consecutive gut biopsies from 30 HLA-B27(+) AS patients, 15 Crohn's disease (CD) patients and 10 normal subjects were obtained. Evidence for HLA-B27 misfolding was studied. Unfolded protein response (UPR) and autophagy were assessed by RT-PCR and immunohistochemistry. The contribution of UPR and autophagy in the regulation of IL-23 expression was evaluated in in vitro experiments on isolated lamina propria mononuclear cells (LPMCs). RESULTS: Intracellular coloca…

SHORT APOB TRUNCATIONS SHOW IMPAIRE CHYLOMICRON EXPORT AND ENTEROCYTE TRIGLYCERIDE ACCUMULATION. IN VIVO AND IN VITRO EVIDENCE ON A APOB 28.25 STABLE-TRANSFECTED ENTEROCYTE CELL LINE

Activated IL-22 pathway occurs in the muscle tissues of patients with polymyositis or dermatomyositis and is correlated with disease activity.

OBJECTIVE: The aim of this study was to assess the expression of IL-22, IL-22 receptor 1 (IL-22R1), IL-22 binding protein (IL-22BP) and p-STAT3 in muscle tissue from patients with PM and DM. METHODS: Levels of IL-22, IL-22R1, IL-22BP and STAT3 mRNA were quantified by RT-PCR. The expression of IL-22, IL-22R1, IL-22BP and p-STAT3 was also analysed using immunohistochemistry. RESULTS: Significant modulation of the IL-22 pathway was observed in inflammatory myopathic tissues. In particular, a significant overexpression of IL-22 at the protein but not the mRNA level was observed in PM/DM tissues and was correlated with myositis activity. IL-22R1 aberrant expression was also observed among infilt…

Type 3 innate lymphoid cells producing IL-17 and IL-22 are expanded in the gut, in the peripheral blood, synovial fluid and bone marrow of patients with ankylosing spondylitis

Background The aim of the study was to better characterise the immunological origin and the behaviour of interleukin (IL)-23-responsive innate lymphoid cells (ILCs) in the gut, synovial fluid (SF) and bone marrow (BM) of patients with ankylosing spondylitis (AS).Methods ILC1, ILC2 and ILC3 cells were determined and characterised by confocal microscopy and flow cytometry in ileal and BM biopsies, in peripheral blood (PB) and SF mononuclear cells obtained from patients with AS and controls. Mucosal vascular addressin cell adhesion molecule 1 (MADCAM-1), IL-7, IL-15 and aggregates of lymphoid tissue inducer cells (LTi) were evaluated by immunohistochemistry. The in vitro ability of epithelial …

IL-9 IN PsA

Objective. To investigate the expression and tis- sue distribution of Th9-related cytokines in patients with psoriatic arthritis (PsA). Methods. Quantitative gene expression analysis of Th1, Th17, and Th9 cytokines was performed in intestinal biopsy samples obtained from patients with PsA, HLA2B272positive patients with ankylosing spondylitis (AS), patients with Crohn’s disease (CD), and healthy controls. Expression and tissue distribu- tion of interleukin-23 (IL-23), IL-17, IL-22, IL-9, and IL-9 receptor (IL-9R) were evaluated by immunohisto- chemistry and confocal microscopy. Flow cytometry was used to study the frequency of Th9 cells among periph- eral blood, lamina propria, and synovial…