Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine: Brussels, Belgium. 15-18 March 2016.

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]

Estrogen Receptor Alpha Is Expressed in Mesenteric Mesothelial Cells and Is Internalized in Caveolae upon Freund's Adjuvant Treatment

Transformation of epithelial cells into connective tissue cells (epithelial-mesenchymal transition, EMT) is a complex mechanism involved in tumor metastasis, and in normal embryogenesis, while type II EMT is mainly associated with inflammatory events and tissue regenaration. In this study we examined type II EMT at the ultrastructural and molecular level during the inflammatory process induced by Freund's adjuvant treatment in rat mesenteric mesothelial cells. We found that upon the inflammatory stimulus mesothelial cells lost contact with the basal lamina and with each other, and were transformed into spindle-shaped cells. These morphological changes were accompanied by release of interleukins IL-1alpha, -1beta and IL-6 and by secretion of transforming growth factor beta (TGF-beta) into the peritoneal cavity. Mesothelial cells also expressed estrogen receptor alpha (ER-alpha) as shown by immunolabeling at the light and electron microscopical levels, as well as by quantitative RT-PCR. The mRNA level of ER-alpha showed an inverse correlation with the secretion of TGF-beta. At the cellular and subcellular levels ER-alpha was colocalized with the coat protein caveolin-1 and was found in the plasma membrane of mesothelial cells, in caveolae close to multivesicular bodies (MVBs) or in the membrane of these organelles, suggesting that ER-alpha is internalized via caveola-mediated endocytosis during inflammation. We found asymmetric, thickened, electron dense areas on the limiting membrane of MVBs (MVB plaques) indicating that these sites may serve as platforms for collecting and organizing regulatory proteins. Our morphological observations and biochemical data can contribute to form a potential model whereby ER-alpha and its caveola-mediated endocytosis might play role in TGF-beta induced type II EMT in vivo

Anti-Inflammatory Preconditioning by Agonists of Adenosine A1 Receptor

BackgroundAdenosine levels rise during inflammation and modulate inflammatory responses by engaging with four different G protein-coupled receptors. It is suggested that adenosine exhibits pro-inflammatory effects through its A(1) receptor (A(1)R), and anti-inflammatory effects through A(2A) receptor (A(2A)R). Therefore, understanding of the mechanisms that govern adenosine receptor regulation may advance treatment of various inflammatory disorders. We previously reported that peak A(1)R expression during leukocyte recruitment, is followed by a peak in A(2A)R during inflammation resolution.Principal findingsHere, we examined whether A(1)R activation sequentially induces A(2A)R expression and by this reverses inflammation. The effect of adenosine on A(1)R mediated A(2A)R expression was examined in peritoneal macrophages (PMPhi) and primary peritoneal mesothelial cells (PMC) in vitro. Induction of A(2A)R was inhibited by pertussis toxin (PTX) and partly dependent on A(2A)R stimulation. Administration of A(1)R agonists to healthy mice reduced A(1)R expression and induced A(2A)R production in PMC. Mice that were preconditioned with A(1)R agonists 24 hours before E. coli inoculation exhibited decreased TNFalpha and IL-6 sera levels and reduced leukocytes recruitment. Preconditioning was blocked by pretreatment with A(1)R antagonist, as well as, or by late treatment with A(2A)R antagonist, and was absent in A(2A)R(-/-) mice.ConclusionsOur data suggest that preconditioning by an A(1)R-agonist promotes the resolution of inflammation by inducing the production of A(2A)R. Future implications may include early treatment during inflammatory disorders or pretreatment before anticipated high risk inflammatory events, such as invasive surgery and organ transplantation