Ecrg4 Attenuates the Inflammatory Proliferative Response of Mucosal Epithelial Cells to Infection

We report an inverse relationship between expression of the orphan candidate tumor suppressor gene esophageal cancer related gene 4 (Ecrg4), and the mucosal epithelial cell response to infection in the middle ear (ME). First, we found constitutive Ecrg4 mRNA expression in normal, quiescent ME mucosa that was confirmed by immunostainning of mucosal epithelial cells and immunoblotting of tissue lysates for the 14 kDa Ecrg4 protein. Upon experimental ME infection, Ecrg4 gene expression rapidly decreased by over 80%, between 3 to 48 hrs, post infection. When explants of this infected mucosa were placed in culture and transduced with an adenovirus (AD) encoding Ecrg4 gene (ADEcrg4), the proliferative and migratory responses of mucosal cells were significantly inhibited. ADEcrg4 transduction of control explants from uninfected MEs had no effect on basal growth and migration. Over-expression of Ecrg4 in vivo, by pre-injecting MEs with ADEcrg4 48 hrs prior to infection, prevented the natural down-regulation of Ecrg4, reduced mucosal proliferation and prevented inflammatory cell infiltration normally observed after infection. Taken together, these data support a hypothesis that Ecrg4 plays a role in coordinating the inflammatory and proliferative response to infection of mucosal epithelium suggesting a possible mechanism for its putative anti-tumor activity.     

Insulin resistance is improved in high‐fat fed mice by photobiomodulation therapy at 630 nm

Photobiomodulation therapy (PBMT) in the infrared spectrum exerts positive effects on glucose metabolism, but the use of PBMT at the red spectrum has not been assessed. Male Swiss albino mice were divided into low‐fat control and high‐fat diet (HFD) for 12 weeks and were treated with red (630 nm) PBMT or no treatment (Sham) during weeks 9 to 12. PBMT was delivered at 31.19 J/cm², 60 J total dose per day for 20 days. In HFD‐fed mice, PBMT improved glucose tolerance, insulin resistance and fasting hyperinsulinemia. PBMT also reduced adiposity and inflammatory infiltrate in adipose tissue. Phosphorylation of Akt in epididymal adipose tissue and rectus femoralis muscle was improved by PBMT. In epididymal fat PBMT reversed the reduced phosphorylation of AS160 and the reduced Glut4 content. In addition, PBMT reversed the alterations caused by HFD in rectus femoralis muscle on proteins involved in mitochondrial dynamics and β‐oxidation. In conclusion, PBMT at red spectrum improved insulin resistance and glucose metabolism in HFD‐fed mice.      

Plagiarism of the host immune system: lessons about chemokine immunology from viruses

In their attempts to evade the host immune response, mammalian viruses have evolved a wide range of strategies. These include the expression and modification of various host cytokines and receptors. Understanding the mechanism of action of these virally encoded proteins will clearly deepen our insights into immunology. In the past few months several new virally encoded chemokines have been described which can modify both the host immune and antiviral response. Their manipulation of the cytokine structure-function relationship may also be useful in the development of reagents for treating immune and proliferative diseases.     

Renal transforming growth factor beta 1 production in neonate rats

Abstract. The newborn rat kidney is not fully developed until approximately 12 days after birth. In order to evaluate the possible role of Transforming Growth Factor beta 1 (TGF beta 1) in renal development we analyzed the mRNA level for TGF beta 1 in sixty Wistar rats aged 1,15 and 30 days. We also performed immunohislochemical studies to visualize the distribution of this peptide in the kidney of these rats using a TGF beta 1 antibody. The results show that the mRNA levels for TGF beta 1 are higher in the kidneys of the 1-day-old rats than in the 15 (1.4 fold) and 30-day-old rats (1.7 fold). The immunohistochemical reaction revealed the presence of TGF beta in the kidneys of the rats. The staining intensity was higher in the renal cortex than in the medulla. The data suggests that TGF beta may be important during kidney development.     

Short-term effects of ACTH on protein synthesis in adrenal cortex cells of young rats

Two units of ACTH were administered intraperitoneally to young 20 gm-rats which received an intravenous injection of L-leucine-3H thirteen min later. ACTH-injected rats, and control rats which received the isotope alone, were killed at 2-, 10-, 30- and 60-min intervals. Electron microscope autoradiographs in control animals showed strong amino-acid uptake at pulse time (2-min) in the cytoplasm of adrenal zona fasciculata cells. Label was shared between the endoplasmic reticulum (ER) and mitochondria, and a lower but still considerable uptake was seen in nucleoli. At first chase time interval (10-min) cytoplasmic labelling declined, while nuclear and nucleolar labelling increased, both changing little thereafter, and there was a 10-30 min Golgi peak. ACTH administration provoked an overall increase in amino-acid incorporation into cytoplasm, nucleus and nucleolus at pulse time, with no changes in the distribution of the reactions among organelles. Intensification of labelling was most evident over nucleoli, the grain density of which was four-times as high as in controls. The short-term increase in ER and mitochondrial protein synthesis observed after ACTH injections was considered to be consistent with the hypothesis that most newly-formed proteins in these cells may be involved in the regulation of steroidogenesis. The marked increase in nucleolar labelling suggested the presence of proteins involved in RNA synthesis.