Vascular cell-adhesion molecule 1 (VCAM-1) regulates JunB-mediated IL-8/CXCL1 expression and pathological neovascularization.

Vascular adhesion molecules play an important role in various immunological disorders, particularly in cancers. However, little is known regarding the role of these adhesion molecules in proliferative retinopathies. We observed that IL-33 regulates VCAM-1 expression in human retinal endothelial cells and that genetic deletion of IL-33 reduces hypoxia-induced VCAM-1 expression and retinal neovascularization in C57BL/6 mice. We found that VCAM-1 via JunB regulates IL-8 promoter activity and expression in human retinal endothelial cells. In addition, our study outlines the regulatory role of VCAM-1-JunB-IL-8 signaling on retinal endothelial cell sprouting and angiogenesis. Our RNA sequencing results show an induced expression of CXCL1 (a murine functional homolog of IL-8) in the hypoxic retina, and intravitreal injection of VCAM-1 siRNA not only decreases hypoxia-induced VCAM-1-JunB-CXCL1 signaling but also reduces OIR-induced sprouting and retinal neovascularization. These findings suggest that VCAM-1-JunB-IL-8 signaling plays a crucial role in retinal neovascularization, and its antagonism might provide an advanced treatment option for proliferative retinopathies.

Long-term exposures to ethion and endotoxin cause lung inflammation and induce genotoxicity in mice.

Ethion, an organophosphorus pesticide, is used worldwide and has potential for toxicity and inflammation. There are very limited data on the pulmonary and genotoxic effects of ethion especially when the exposure is combined with lipopolysaccharide. Therefore, we used a mouse model to test the hypothesis that prolonged exposure to ethion alone or in conjunction with lipopolysaccharide (LPS) will cause lung inflammation and genotoxicity in a mouse model. Swiss albino (n = 30) were divided into a control (n = 10) and two treatment groups (n = 10; each group). The treatment groups were orally administered ethion (4 or 2 mg/kg/animal/day; n = 10 each) dissolved in corn oil for 90 days. After 90 days of exposure, five animals from each of the groups were challenged with 80 µg Escherichia coli lipopolysaccharide (LPS) intranasally and the remaining five animals with normal saline solution via the same route. Ethion at both dosages induced lung inflammation as indicated by increased (p < 0.05) perivascular and peribronchial accumulation of inflammatory cells along with thickening of the alveolar septal wall. Ethion at 4 mg/kg altered (p < 0.05) the mRNA and protein expression of TLR-9 and IL-1ß in the lungs and induced genotoxicity in blood cells as determined by single cell gel electrophoresis (Comet assay). Further, both dosages of ethion in combination with E. coli LPS caused genotoxicity and increased (p < 0.05) pulmonary expression of TLR-4, TLR-9 and IL-1ß. The data taken together suggest ethion induces lung inflammation and interaction between ethion and LPS increases genotoxicity in blood cells.

Long non-coding RNA: its evolutionary relics and biological implications in mammals: a review.

The central dogma of gene expression propounds that DNA is transcribed to mRNA and finally gets translated into protein. Only 2-3% of the genomic DNA is transcribed to protein-coding mRNA. Interestingly, only a further minuscule part of genomic DNA encodes for long non-coding RNAs (lncRNAs) which are characteristically more than 200 nucleotides long and can be transcribed from both protein-coding (e.g. H19 and TUG1) as well as non-coding DNA by RNA polymerase II. The lncRNAs do not have open reading frames (with some exceptions), 3`-untranslated regions (3'-UTRs) and necessarily these RNAs lack any translation-termination regions, however, these can be spliced, capped and polyadenylated as mRNA molecules. The flexibility of lncRNAs confers them specific 3D-conformations that eventually enable the lncRNAs to interact with proteins, DNA or other RNA molecules via base pairing or by forming networks. The lncRNAs play a major role in gene regulation, cell differentiation, cancer cell invasion and metastasis and chromatin remodeling. Deregulation of lncRNA is also responsible for numerous diseases in mammals. Various studies have revealed their significance as biomarkers for prognosis and diagnosis of cancer. The aim of this review is to overview the salient features, evolution, biogenesis and biological importance of these molecules in the mammalian system.