IL-9 Induces VEGF Secretion from Human Mast Cells and IL-9/IL-9 Receptor Genes Are Overexpressed in Atopic Dermatitis

Interleukin 9 (IL-9) has been implicated in mast cell-related inflammatory diseases, such as asthma, where vascular endothelial growth factor (VEGF) is involved. Here we report that IL-9 (10–20 ng/ml) induces gene expression and secretion of VEGF from human LAD2. IL-9 does not induce mast cell degranulation or the release of other mediators (IL-1, IL-8, or TNF). VEGF production in response to IL-9 involves STAT-3 activation. The effect is inhibited (about 80%) by the STAT-3 inhibitor, Stattic. Gene-expression of IL-9 and IL-9 receptor is significantly increased in lesional skin areas of atopic dermatitis (AD) patients as compared to normal control skin, while serum IL-9 is not different from controls. These results imply that functional interactions between IL-9 and mast cells leading to VEGF release contribute to the initiation/propagation of the pathogenesis of AD, a skin inflammatory disease

The Diagnostic, Prognostic and Therapeutic Role of miRNAs in Adrenocortical Carcinoma: A Systematic Review

Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with a dismal prognosis and a high rate of recurrence and mortality. Therapeutic options are limited. In some cases, the distinction of ACCs from benign adrenal neoplasms with the existing widely available pathological and histopathological tools is difficult. Thus, new biomarkers have been tested. We conducted a review of the recent literature on the advances of the diagnostic, prognostic and therapeutic role of miRNAs on ACC patients. More than 10 miRNAs validated by multiple studies were found to present a diagnostic and prognostic role for ACC patients, from which miR-483-5p and miR-195 were the most frequently met biomarkers. In particular, upregulation of miR-483-5p and downregulation of miR-195 were the most commonly validated molecular alterations. Unfortunately, data on the therapeutic role of miRNA are still scarce and limited mainly at the experimental level. Thus, the role of miRNA regulation in ACC remains an area of active research

IL-9 Induces VEGF Secretion from Human Mast Cells and IL-9/IL-9 Receptor Genes Are Overexpressed in Atopic Dermatitis

Interleukin 9 (IL-9) has been implicated in mast cell-related inflammatory diseases, such as asthma, where vascular endothelial growth factor (VEGF) is involved. Here we report that IL-9 (10-20 ng/ml) induces gene expression and secretion of VEGF from human LAD2. IL-9 does not induce mast cell degranulation or the release of other mediators (IL-1, IL-8, or TNF). VEGF production in response to IL-9 involves STAT-3 activation. The effect is inhibited (about 80%) by the STAT-3 inhibitor, Stattic. Gene-expression of IL-9 and IL-9 receptor is significantly increased in lesional skin areas of atopic dermatitis (AD) patients as compared to normal control skin, while serum IL-9 is not different from controls. These results imply that functional interactions between IL-9 and mast cells leading to VEGF release contribute to the initiation/propagation of the pathogenesis of AD, a skin inflammatory disease

IL-9 serum level in AD patients (n = 18) and controls (n = 39).

<p>IL-9 level was determined using Millipex microbead assay and the measurements were performed blind by Millipore (St. Charles, MI).</p

(A) IL-9 induces STAT3 phosphorylation in LAD2 cells.

<p>Cells were stimulated with IL-9 for up to 20 min. Phospho-STAT3 levels in the cell lysates were determined by ELISA. (B) STAT3 inhibitor Stattic inhibits IL-9-induced VEGF release from LAD2 cells. LAD2 cells were pre-incubated for 30 min with the indicated concentrations of Stattic. Cells were stimulated with IL-9 (10–20 ng/ml) for 24 h and supernatant VEGF was measured by ELISA. Data are representative of similar experiments.</p

(A) IL-9 gene expression in the skin of AD affected (n = 16) and normal healthy controls (n = 12).

<p>(B) IL-9 receptor (IL-9r) gene expression in skin of AD affected (n = 19) skin and normal healthy controls (n = 20). Relative quantities of mRNA expression were measured by quantitative RT-PCR and normalized to GAPDH. TaqMan was performed with cDNA reverse transcribed from 100 ng RNA from each sample. *p<0.05.</p

IL-9 stimulates VEGF production in human mast cells.

<p>(A) Gene expression. LAD2 cells were stimulated with IL-9 for 6 hrs, RNA was extracted and relative VEGF mRNA levels were determined by real-time PCR. (B) Protein release. LAD2 cells were stimulated with the indicated concentration of IL-9 (10–20 ng/ml) for 48 hrs. VEGF was measured in the supernatant fluid by ELISA. Data are the mean ± SD of 3 separate experiments performed in triplicate (*<i>P</i><0.05 versus unstimulated cells).</p

Mitochondrial dysfunction in affected skin and increased mitochondrial DNA in serum from patients with psoriasis

Psoriasis is characterized by keratinocyte proliferation and chronic inflammation, but the pathogenesis is still unclear. Dysregulated mitochondria (mt) could lead to reduced apoptosis and extracellular secretion of mtDNA, acting as “innate pathogen” triggering inflammation. Serum was obtained from healthy volunteers and psoriatic patients. Mitochondrial DNA was extracted from the serum and amplified with quantitative PCR (qPCR). Punch biopsies were obtained from lesional and non-lesional psoriatic skin (10 cm apart) and from healthy volunteers, were placed in RNA later and were stored at -80 degrees C until RNA was extracted and cDNA was synthesized; gene expression of uncoupling protein 2 (UCP2), Dynamin-related protein 1 (Drp1) and calcineurin, involved in the regulation of mitochondria function, was detected with qPCR. Mitochondrial DNA was significantly increased (7s, P = 0.0496 and Cytochrome B, CytB, P = 0.0403) in the serum of psoriatic patients (n = 63) as compared to controls (n = 27). Gene expression was significantly reduced for UCP2 (P = 0.0218), Drp1 (P = 0.0001) and calcineurin (P = 0.0001) in lesional psoriatic skin, as compared to non-lesional or control skin. Increased serum extracellular mtDNA in psoriatic patients and decreased expression of mitochondrial regulatory proteins in psoriatic skin suggest increased inflammation and reduced keratinocyte apoptosis, respectively. Inhibitors of mtDNA secretion and/or UCP2 stimulants may be potential treatment options