Analysis of differential expression of protease-activated receptors in patients with allergic fungal rhinosinusitis

Background Ever since its characterization in the 1970s, allergic fungal rhinosinusitis (AFRS) has been the subject of much controversy, especially regarding its pathogenesis. In this study, we analyzed the differential expression of genes that encode protease-activated receptors (PAR) in patients with AFRS and patients with chronic rhinosinusitis, and tried to understand the pathogenic basis of this disease. Objective To analyze the differential expression of PAR genes in patients with AFRS and in patients with chronic rhinosinusitis. Methods Mucosa from ethmoid sinuses of 51 patients (tests and controls) was biopsied and evaluated for messenger RNA expression of PAR genes by using reverse transcriptase–polymerase chain reaction. Each of the four PAR genes, i.e., par1, par2, par3 and par4 was amplified, the final gene products were run on 1.8% agarose gel and analyzed by densitometry to calculate differential expression. The significance level was determined as p ≤ 0.05. Results It was observed that the expressions of all four par genes were higher in the test samples compared with the controls, but statistical significance was achieved only for par1 (p=0.004) and par2 (p=0.05). Comparative expression of the four PAR genes was also performed within the test and control groups, and a statistically significant difference was seen between par1 and par2 (p=0.007), par1 and par3 (p=0.029), par1 and par4 (p=0.0001), par2 and par4 (p=0.002), and par3 and par4 (p=0.009) in the test group. In the control group as well, par1, par2, and par3 exhibited a higher expression compared with par4 but the difference was significant between par3 and par4 genes only. Conclusion Patients with AFRS expressed increased levels of PAR genes in their nasal mucosa, and, of the four PAR genes, a higher expression of par1, par2, and par3 was observed in both the groups compared with par4. This information contributes toward our understanding of pathogenesis and possibly treatment of AFRS

Interleukin 17 promotes angiotensin II-induced hypertension and vascular dysfunction

We have shown previously that T cells are required for the full development of angiotensin II–induced hypertension. However, the specific subsets of T cells that are important in this process are unknown. T helper 17 cells represent a novel subset that produces the proinflammatory cytokine interleukin 17 (IL-17). We found that angiotensin II infusion increased IL-17 production from T cells and IL-17 protein in the aortic media. To determine the effect of IL-17 on blood pressure and vascular function, we studied IL-17−/− mice. The initial hypertensive response to angiotensin II infusion was similar in IL-17−/− and C57BL/6J mice. However, hypertension was not sustained in IL-17−/− mice, reaching levels 30-mm Hg lower than in wild-type mice by 4 weeks of angiotensin II infusion. Vessels from IL-17−/− mice displayed preserved vascular function, decreased superoxide production, and reduced T-cell infiltration in response to angiotensin II. Gene array analysis of cultured human aortic smooth muscle cells revealed that IL-17, in conjunction with tumor necrosis factor-α, modulated expression of >30 genes, including a number of inflammatory cytokines/chemokines. Examination of IL-17 in diabetic humans showed that serum levels of this cytokine were significantly increased in those with hypertension compared with normotensive subjects. We conclude that IL-17 is critical for the maintenance of angiotensin II–induced hypertension and vascular dysfunction and might be a therapeutic target for this widespread disease

CD70 exacerbates blood pressure elevation and renal damage in response to repeated hypertensive stimuli

RATIONALE: Accumulating evidence supports a role of adaptive immunity and particularly T cells in the pathogenesis of hypertension. Formation of memory T cells, which requires the costimulatory molecule CD70 on antigen-presenting cells, is a cardinal feature of adaptive immunity. OBJECTIVE: To test the hypothesis that CD70 and immunologic memory contribute to the blood pressure elevation and renal dysfunction mediated by repeated hypertensive challenges. METHODS AND RESULTS: We imposed repeated hypertensive challenges using either N(ω)-nitro-L-arginine methyl ester hydrochloride (L-NAME)/high salt or repeated angiotensin II stimulation in mice. During these challenges effector memory T cells (T(EM)) accumulated in the kidney and bone marrow. In the L-NAME/high-salt model, memory T cells of the kidney were predominant sources of interferon-γ and interleukin-17A, known to contribute to hypertension. L-NAME/high salt increased macrophage and dendritic cell surface expression of CD70 by 3- to 5-fold. Mice lacking CD70 did not accumulate T(EM) cells and did not develop hypertension to either high salt or the second angiotensin II challenge and were protected against renal damage. Bone marrow-residing T(EM) cells proliferated and redistributed to the kidney in response to repeated salt feeding. Adoptively transferred T(EM) cells from hypertensive mice homed to the bone marrow and spleen and expanded on salt feeding of the recipient mice. CONCLUSIONS: Our findings illustrate a previously undefined role of CD70 and long-lived T(EM) cells in the development of blood pressure elevation and end-organ damage that occur on delayed exposure to mild hypertensive stimuli. Interventions to prevent repeated hypertensive surges could attenuate formation of hypertension-specific T(EM) cell

Avian influenza A (H5N1) outbreaks in different poultry farm types in Egypt: The effect of vaccination, closing status and farm size

Background: The Avian Influenza A (H5N1) virus is endemic in poultry in Egypt. The winter of 2014/2015 was particularly worrying as new clusters of HPAI A (H5N1) virus emerged, leading to an important number of AI A (H5N1) outbreaks in poultry farms and sporadic human cases. To date, few studies have investigated the distribution of HPAI A (H5N1) outbreaks in Egypt in relation to protective / risk factors at the farm level, a gap we intend to fill. The aim of the study was to analyse passive surveillance data that were based on observation of sudden and high mortality of poultry or drop in duck or chicken egg production, as a basis to better understand and discuss the risk of HPAI A (H5N1) presence at the farm level in large parts of the Nile Delta. Results: The probability of HPAI A (H5N1) presence was associated with several characteristics of the farms. Vaccination status, absence of windows/openings in the farm and the number of birds per cycle of production were found to be protective factors, whereas the presence of a duck farm with significant mortality or drop in egg production in the village was found to be a risk factor. Conclusions: Results demonstrate the key role of several prevention and biosecurity measures to reduce HPAI A (H5N1) virus circulation, which could promote better poultry farm biosecurity in Egypt.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Interleukin-17A is associated with flow-mediated dilation and interleukin-4 with carotid plaque in persons with HIV

Objective: Chronic inflammation contributes to the high burden of cardiovascular disease (CVD) in persons with HIV (PWH). HIV has broad effects on innate and adaptive immune cells, including innate lymphoid cells (ILCs) and CD4+ T-helper cells. At present, the relationship between CVD and plasma cytokines reflecting ILC/T-helper responses in PWH is not well defined. We investigated relationships between plasma cytokines and subclinical atherosclerosis. Design: A cross-sectional study. Methods: We recruited 70 PWH on a single antiretroviral regimen (efavirenz, teno- fovir, and emtricitabine) with at least 12 months of suppressed viremia and 30 HIVnegative controls. We quantified plasma cytokines and chemokines, including inter- feron-g, interleukin (IL)-4, IL-13, and IL-17A, markers of macrophage activation, and markers of endothelial activation using multiplex assays and ELISA. Cytokines were grouped using Ward's hierarchical clustering. Brachial artery flow-mediated dilation (FMD) and carotid plaque burden were determined using ultrasound. Multivariable linear regression and negative binomial regression analyses were used to assess the relationships of plasma biomarkers and endpoints adjusted for CVD risk factors. Results: We identified three distinct clusters in PWH, one containing Th1/Th2/ILC1/ ILC2 type cytokines, one with Th17/ILC3/macrophage-related cytokines, and a less specific third cluster. Lower FMD was associated with higher plasma IL-17A and macrophage inflammatory protein-1 a. In contrast, IL-4, a Th2/ILC2 type cytokine, was associated with carotid plaque. When HIV-negative controls were added to the models clustering was more diffuse, and these associations were attenuated or absent. Conclusion: Th17/ILC3 and Th2/ILC2-mediated immune mechanisms may have distinct roles in endothelial dysfunction and atherosclerotic plaque formation, respectively, in PWH

Changing geographic patterns and risk factors for avian influenza A(H7N9) infections in humans, China

The fifth epidemic wave of avian influenza A(H7N9) virus in China during 2016-2017 demonstrated a geographic range expansion and caused more human cases than any previous wave. The factors that may explain the recent range expansion and surge in incidence remain unknown. We investigated the effect of anthropogenic, poultry, and wetland variables on all epidemic waves. Poultry predictor variables became much more important in the last 2 epidemic waves than they were previously, supporting the assumption of much wider H7N9 transmission in the chicken reservoir. We show that the future range expansion of H7N9 to northern China may increase the risk of H7N9 epidemic peaks coinciding in time and space with those of seasonal influenza, leading to a higher risk of reassortments than before, although the risk is still low so far.SCOPUS: ar.jinfo:eu-repo/semantics/publishe