Epstein-Barr virus.

The importance of the gut-brain axis in maintaining homeostasis has long been appreciated. However, the past 15 yr have seen the emergence of the microbiota (the trillions of microorganisms within ...

The Microbiota-Gut-Brain Axis

▪ Abstract This review deals with membrane Fc receptors (FcR) of the immunoglobulin superfamily. It is focused on the mechanisms by which FcR trigger and regulate biological responses of cells on which they are expressed. FcR deliver signals when they are aggregated at the cell surface. The aggregation of FcR having immunoreceptor tyrosine-based activation motifs (ITAMs) activates sequentially src family tyrosine kinases and syk family tyrosine kinases that connect transduced signals to common activation pathways shared with other receptors. FcR with ITAMs elicit cell activation, endocytosis, and phagocytosis. The nature of responses depends primarily on the cell type. The aggregation of FcR without ITAM does not trigger cell activation. Most of these FcR internalize their ligands, which can be endocytosed, phagocytosed, or transcytosed. The fate of internalized receptor-ligand complexes depends on defined sequences in the intracytoplasmic domain of the receptors. The coaggregation of different FcR result...

Fc RECEPTOR BIOLOGY

http://cellbanktech.com/wp-content/uploads/2014/02/10.-Meirelles-LD-et-al.-Mechanisms-involved-in-therapeutic-properties-of-mesenchymal-stem-cells.-in-Cytokine-Growth-Factor-Res-2009.pdf

Mechanisms involved in the therapeutic properties of mesenchymal stem cells

Immunomodulation of autoimmune and inflammatory diseases with intravenous immune globulin.

Ten years ago M. Kazatchkine, U. Nydegger, and Y. Sultan decided to treat patients with acquired hemophilia using intravenous immunoglobulins (IVIg). This was during a meeting in Denmark about autoimmune diseases and IVIg. In 1983, several authors had reported on the efficacy of IVIg in autoimmune diseases such as idiopathic thrombocytopenic purpura in children1,2 and adults,3 immune neutropenia,2,4 and red cell aplasia.5 Autoantibodies to factor VIII (F.VIII) occurring in either otherwise healthy patients or during the course of a more characterized immune disorder such as disseminated lupus erythematosus (DUE) and rheumatoid polyarthritis seemed to be good models. One major reason is that the neutralizing capacity of autoantibodies to F.VIII is easily and reproducibly quantified using the Bethesda assay, while this is not the case in most of the autoimmune diseases mentioned above.

IVIg in the treatment of patients with factor VIII inhibitors

Activity-based probes (ABP) are molecules that bind covalently to the active form of an enzyme family, making them an attractive tool for target and biomarker identification and drug discovery. The present study describes the synthesis and biochemical characterization of novel activity-based probes targeting trypsin-like serine proteases. We developed an extensive library of activity-based probes with “clickable” affinity tags and a diaryl phosphonate warhead. A wide diversity was achieved by including natural amino acid analogs as well as basic polar residues as side chains. A detailed enzymatic characterization was performed in a panel of trypsin-like serine proteases. Their inhibitory potencies and kinetic profile were examined, and their IC50 values, mechanism of inhibition, and kinetic constants were determined. The activity-based probes with a benzyl guanidine side chain showed the highest inhibitory effects in the panel. Surprisingly, some of the high-affinity probes presented a reversible inhibitory mechanism. On the other hand, probes with different side chains exhibited the expected irreversible mechanism. For the first time, we demonstrate that not only irreversible probes but also reversible probes can tightly label recombinant proteases and proteases released from human mast cells. Even under denaturing SDS-PAGE conditions, reversible slow-tight-binding probes can label proteases due to the formation of high-affinity complexes and slow dissociation rates. This unexpected finding will transform the view on the required irreversible nature of activity-based probes. The diversity of this library of activity-based probes combined with a detailed enzyme kinetic characterization will advance their applications in proteomic studies and drug discovery.

Chemically diverse activity-based probes with unexpected inhibitory mechanisms targeting trypsin-like serine proteases

Presence of IgG exhibiting a morphine-like activity in therapeutic intravenous immunoglobulins.

Background: Peritoneal carcinomatosis often results in alterations in intestinal peristalsis and recurrent abdominal pain. Pain management in these patients is often unsatisfactory. This study aimed to investigate whether endothelin-1 (EDN1) was involved in pain mediation in peritoneal carcinomatosis, and thus whether the EDN1 pathway could be a new therapeutic target for peritoneal carcinomatosis-associated pain. Methods: EDN1 plasma levels and abdominal pain severity were assessed in patients with abdominal tumors, with or without peritoneal carcinomatosis, and in healthy donors. The effects of EDN1 on the visceromotor response to colorectal distension, and on colonic contractions were then examined in mice, and the mechanism of action of EDN1 was then investigated by measuring the impact of EDN1 exposure on calcium mobilization in cultured neurons. Inhibition studies were also performed to determine if the effects of EDN1 exposure could be reversed by EDN1-specific receptor antagonists. Results: A positive correlation between EDN1 plasma levels and abdominal pain was identified in patients with peritoneal carcinomatosis. EDN1 exposure increased visceral sensitivity and the amplitude of colonic contractions in mice and induced calcium mobilization by direct binding to its receptors on sensory neurons. The effects of EDN1 were inhibited by antagonists of the EDN1 receptors. Conclusions: This preliminary study, using data from patients with peritoneal carcinomatosis combined with data from experiments performed in mice, suggests that EDN1 plays a key role mediating pain in peritoneal carcinomatosis. Our findings suggest that antagonists of the EDN1 receptors might be beneficial in the management of pain in patients with peritoneal carcinomatosis.

/pdf/endothelin-1-exhibiting-pro-nociceptive-and-pro-peristaltic-zikr6ss63x.pdf

Endothelin-1 Exhibiting Pro-Nociceptive and Pro-Peristaltic Activities Is Increased in Peritoneal Carcinomatosis

La sensation douloureuse est une caractéristique de l’inflammation aiguë qui se développe lors d’une infection. Cette douleur s’estompe quelques jours après l’infection, lorsque les lymphocytes T effecteurs générés en réponse aux antigènes microbiens gagnent le site inflammatoire. Cette régulation de la douleur inflammatoire est tributaire de la libération locale d’opioïdes endogènes par les lymphocytes T et de leur action sur les nocicepteurs en périphérie. Ce phénomène pourrait expliquer pourquoi un certain nombre de patients atteints de maladies inflammatoires chroniques de l’intestin ne ressentent pas systématiquement des douleurs abdominales ou qu’elles ne font pas toujours partie du tableau clinique initial.

Gilles Dietrich

Papers

IVIg in the treatment of patients with factor VIII inhibitors

Chemically diverse activity-based probes with unexpected inhibitory mechanisms targeting trypsin-like serine proteases

Presence of IgG exhibiting a morphine-like activity in therapeutic intravenous immunoglobulins.

Endothelin-1 Exhibiting Pro-Nociceptive and Pro-Peristaltic Activities Is Increased in Peritoneal Carcinomatosis

Régulation de la douleur inflammatoire viscérale par les opioïdes d’origine lymphocytaire