Prominent Chronic Inflammation Research Articles

Inflammatory Cells Can Alter the Levels of H3K9ac and γH2AX in Dysplastic Cells and Favor Tumor Phenotype.

Oral potentially malignant disorders (OPMD) are clinical presentations that carry an increased risk of cancer development. Currently, epithelial dysplasia grade is based on architectural and cytological epithelial changes and is used to predict the malignant transformation of these lesions. However, predicting which OPMD will progress to a malignant tumor is very challenging. Inflammatory infiltrates can favor cancer development, and recent studies suggest that this association with OPMD lesions may be related to the etiology and/or aggressive clinical behavior of these lesions. Epigenetic changes such as histone modifications may mediate chronic inflammation and also favor tumor cells in immune resistance and evasion. This study aimed to evaluate the relationship between histone acetylation (H3K9ac) and DNA damage in the context of dysplastic lesions with prominent chronic inflammation. Immunofluorescence of "low-risk" and "high-risk" OPMD lesions (n = 24) and inflammatory fibrous hyperplasia (n = 10) as the control group was performed to assess histone acetylation levels and DNA damage through the phosphorylation of H2AX (γH2AX). Cell co-culture assays with PBMCs and oral keratinocyte cell lines (NOK-SI, DOK, and SCC-25) were performed to assess proliferation, adhesion, migration, and epithelial-mesenchymal transition (EMT). Oral dysplastic lesions showed a hypoacetylation of H3K9 and low levels of γH2AX compared to control. The contact of dysplastic oral keratinocytes with PBMCs favored EMT and the loss of cell-cell adhesion. On the other hand, p27 levels increased and cyclin E decreased in DOK, indicating cell cycle arrest. We conclude that the presence of chronic inflammation associated to dysplastic lesions is capable of promoting epigenetic alterations, which in turn can favor the process of malignant transformation.

IL-27/IL-27RA signaling may modulate inflammation and progression of benign prostatic hyperplasia via suppressing the LPS/TLR4 pathway.

BackgroundBenign prostatic hyperplasia (BPH) is the most common urologic disease affecting aging men. The pathogenesis of BPH is multi-factorial, and chronic inflammation (CI) might be the central mechanism. Interleukin (IL)-27 signaling has been suggested as a modulator in autoimmune and inflammatory conditions. In this study, we used microarray experiments to analyze gene expression and molecular phenotypic associated with BPH progression, with a particular focus on CI and IL-27/IL-27RA signaling, and verified the microarray data in cell biology experiments.MethodsThirty BPH patients’ specimens and clinical parameters were analyzed. BPH patients were divided into two groups based on the average prostate volume (41.5 mL): group 1, ≤40 mL; and group 2, >40 mL. Microarray experiments were conducted to identify differentially expressed genes (DEGs) by applying appropriate biostatistics to normalize and analyze the dataset. The candidate gene (IL27RA) was validated by quantitative reverse transcriptase-PCR (qRT-PCR) and immunohistochemistry (IHC). The interaction of IL27RA with genes involved in canonical inflammation-associated pathways was investigated by cell biology experiments.ResultsEighty-three percent of BPH specimens contained inflammatory infiltrates, and the predominant type was CI. The serum PSA levels and prevalence of CI were higher in group 2. Microarray experiments identified 361 DEGs between these 2 groups. IL27RA was down-regulated and associated with prominent CI in BPH tissues of group 2. Validated by qRT-PCR and IHC, the results showed IL-27RA might modulate CI and progression of BPH. Thus, we investigated the interaction of IL27RA with TLR4, IL6, and IL8, which were involved in inflammation-associated pathways. We found the activation of IL-27RA after IL-27 treatment led to phosphorylation of STAT1 and STAT3 in prostate epithelial cells. By comparative treatments with lipopolysaccharide (LPS), IL-27, or combination, we found that IL-27/IL-27RA signaling suppressed the production of inflammatory cytokines, IL-6 and IL-8, induced by LPS/TLR4 pathway.ConclusionsOur study revealed that down-regulation of IL27RA in prostate tissue was associated with higher prevalence of CI and BPH progression. IL-27/IL-27RA signaling suppressed the LPS/TLR4 pathway. We conclude the IL-27/IL-27RA signaling might modulate CI and provide potential therapeutic strategies to prevent BPH progression.

Laryngeal polyp associated with reflux disease: a\xa0case report

BackgroundAmong the most common benign laryngeal lesions are vocal nodules and polyps. Their etiology is related to vocal abuse. Gastroesophageal reflux disease is a common condition presenting with a broad spectrum of symptoms, among which are extraesophageal manifestations such as laryngeal polyps.Case presentationA 24-year-old Middle Eastern woman presented to the author’s institution with dysphonia and dyspepsia. She underwent endoscopy and was diagnosed with severe reflux disease. In addition, laryngoscopy revealed a polyp at the left vocal cord, and the patient underwent polypectomy. Histopathological examination revealed a laryngeal polyp of telangiectatic type characterized by hyperplastic epithelial covering with reactive atypia, prominent superficial acanthosis with neutrophils, and prominent chronic inflammation and thrombosed vessels in the stroma.ConclusionThis report focuses on the pathological findings associated with a laryngeal polyp in a young patient diagnosed with severe reflux disease. Acknowledging such characteristic changes in a laryngeal polyp could aid in the diagnosis of gastroesophageal reflux disease.

A pro-tumorigenic function of S100A8/A9 in carcinogen-induced hepatocellular carcinoma

Human hepatocellular carcinoma (HCC) is a heterogeneous disease, driven by different risk factors and presenting diverse clinicopathological features and outcomes. Epidemiological and experimental data indicate that the damage-associated molecular pattern molecules S100A8 and S100A9, forming a heterodimer called calprotectin, might be critically involved in HCC development. However, deletion of S100a9 in an inflammation- and cirrhosis-driven mouse model did not show any impairment in liver tumorigenesis, most likely due to functional compensation by other inflammatory cytokines. Here, we investigated the effect of calprotectin ablation in mice treated with diethylnitrosamine, a carcinogen-driven HCC model mimicking cancer development caused by acute liver damage in the absence of prominent chronic inflammation and tissue damage. We found that tumor cell proliferation was diminished in the absence of S100A8/A9, leading to significant reduction of tumor size.Our results demonstrate that calprotectin is required for the progression of non-inflammation driven liver tumor and might represent a therapeutic target for the treatment of HCC formed in non-cirrhotic liver.

Pericardial Delayed Hyperenhancement With CMR Imaging in Patients With Constrictive Pericarditis Undergoing Surgical Pericardiectomy: A Case Series With Histopathological Correlation

The purpose of this study was to examine the prevalence and histopathologic correlates of pericardial delayed hyperenhancement (DHE) seen with cardiac magnetic resonance imaging (CMR) among patients with constrictive pericarditis (CP) undergoing pericardiectomy. Constrictive pericarditis patients studied by CMR will occasionally demonstrate pericardial DHE following gadolinium contrast administration. We identified 25 CP patients who underwent pericardiectomy following CMR-gadolinium study. We also assessed 10 control subjects with no evidence of pericardial disease referred for cardiac viability imaging. A novel 14-segment pericardial model was used to determine pericardial DHE score and thickness score. Histopathology of pericardial specimens was reviewed and evaluated semiquantitatively on a 4-point scale for the extent of calcification, fibrosis, inflammation, and neovascularization. DHE was present in 12 (48%) CP patients (DHE+ group), and absent in 13 CP patients (DHE- group) and all control patients. The DHE+ group had greater fibroblastic proliferation and neovascularization, as well as more prominent chronic inflammation and granulation tissue. Fibroblastic proliferation and chronic inflammation correlated with DHE presence quantitated by DHE score (Spearman r = 0.578, p < 0.002, and r = 0.590, p < 0.002, respectively), but not with pericardial thickness. Segmental analysis demonstrated no significant difference in the percentage of patients with different pericardial segmental thickness; however, overall, in each segment, the DHE+ group tended to have greater pericardial thickness. The presence of pericardial DHE on CMR is common in patients with CP, and its presence is associated with histological features of organizing pericarditis, which may be a target for future focused pharmacological interventions. Patients with CP without pericardial DHE had more pericardial fibrosis and calcification, as well as lesser degrees of pericardial thickening.

The naked fox: hypotrichosis in arctic foxes (Alopex lagopus)

We describe the manifestations and occurrence of hypotrichosis in arctic foxes and compare it to the Samson character in red foxes. During 1979–2005, we collected carcasses of both normal and hypotrichotic arctic foxes from foxhunters in Iceland for macroscopic and microscopic examination and study of demography. We obtained live pups for breeding and transmission experiments in captivity during 1985–1992. Placental scar counts showed that hypotrichotic vixens were more fertile than normal vixens and generally all their pups were hypotrichotic. Fertility in hypotrichotic vixens was positively correlated with winter air temperature but not in normal vixens. Hypotrichotic males were less likely to breed than normal males and probably had a higher mortality rate than either hypotrichotic females or normal foxes. Hypotrichosis can be transmitted between adult foxes. Microscopic examination revealed prominent chronic inflammation of the dermis in hypotrichotic specimens, degenerative changes, vacuolisation and necrosis of hair follicles. Hypotrichosis persists in coastal areas with mild winters and may become more common with global warming.

ATYPICAL WEGENERʼS GRANULOMATOSIS PRESENTING AS LACRIMAL GLAND ENLARGEMENT AND OPHTHALMIC VENOUS OUTFLOW OBSTRUCTION CAUSING SECONDARY GLAUCOMA IN A MAN WITH A PRIOR PAROTIDECTOMY.

Purpose of Study Report occurrence of Wegener9s granulomatosis presenting as ophthalmic venous outflow obstruction causing secondary glaucoma in a man with a prior parotidectomy. Methods Used Retrospective case study. Summary of Results A 52-year-old man with diabetes mellitus presented with a red, painful eye. The patient denied dry eyes or dry mouth and otherwise felt well. There was no weight loss, fever, or night sweats. A year earlier, he had had left parotidectomy, which showed nonspecific chronic inflammation. On examination, the intraocular pressure was elevated, and there was episcleral injection, suggesting orbital or ophthalmic venous obstruction causing glaucoma. Magnetic resonance imaging of the brain and orbits showed prominence of the left lacrimal gland and subtle signs of venous congestion bilaterally. Biopsy showed a benign lymphoepithelial lesion with prominent chronic inflammation between acini and ducts, composed of lymphocytes, plasma cells, and eosinophils without granulomata. Later the patient complained of sinus congestion. CT of the sinuses showed septal deviation to the left and enlarged inferior turbinates. There were no intranasal lesions. A Schirmer9s test showed no xerophthalmia, and the oral mucosa was normal. The antiproteinase 3 antibody was > 6 (positive), suggestive of Wegener9s granulomatosis. The antinuclear antibody was weakly positive at 1:40, speckled; the anti-smRNP antibody was 9 (equivocal). The rheumatoid factor was negative. The anti-dsDNA, antimyeloperoxidase, anti-Smith, and SS-A (anti-Ro) and SS-B (anti-La) antibodies were negative; the angiotensin-converting enzyme was within normal limits. Despite therapy with prednisone, the patient developed uveitis and scleritis in both eyes and ultimately responded to therapy with oral cyclophosphamide. The patient was well and chose to stop therapy after 3 years. Conclusions Systemic vasculitis may present with tumor-like lesions.1 Retro-orbital pseudotumors, scleritis, and unilateral parotid enlargement are known Wegener9s manifestations.2,3 The present patient had unilateral parotitis, acute glaucoma secondary to orbital venous outflow obstruction, lacrimal enlargement, and, later, uveitis reflecting regional inflammation. The anti-proteinase 3 antibody suggested Wegener9s granulomatosis. 1. Medicine 2000;79:349-59. 2. Mayo Clin Proc 1990;65:1110-7. 3. Laryngoscope 2004;114:1730-3.

THE ATYPICAL COLITIDES

Collangenous colitis is a clinicopathologic syndrome characterized by (1) chronic watery diarrhea and crampy abdominal pain and (2) distinctive colorectal histopathology that includes a subepithelial collagen band, prominent chronic inflammation in the lamina propria, and increased intraepithelial lymphocytes. Lymphocytic colitis has similar clinical features to collangenous colitis, the main symptom being chronic watery diarrhea. Diversion colitis is an inflammatory process that arises in segments of the large intestine that are excluded from the fecal stream. This condition usually occurs in patients with ileostomy or colostomy when a mucous fistula or Hartmann's pouch has been left.