Dose dependent inhibition of B-16 melanoma growth in vivo by a synthetic analogue of PGE2

Daily intratumor administration of 16,16-dimethyl-PGE2-methyl ester in two different dosages inhibited tumor growth in C57Bl/6J mice bearing subcutaneous B-16 melanomas. The larger dose (20 microgram/day/mouse) produced a 68% decrease in tumor volume, a 69% decrease in tumor weight and a 60% decrease in the number of cells in mitotic phase. The smaller dose (10microgram/day/mouse) was one fifth less effective than the 20microgram dose but produced similar changes. Histological examination of tumors revealed no significant differences either in the inflammatory cell population or the amount of necrosis in the control and di-M-PGE2-treated tumors.     

Nod2 Activates NF-kB in CD4+ T Cells but Its Expression Is Dispensable for T Cell-Induced Colitis

Although the etiology of Crohn''s disease (CD) remains elusive this disease is characterized by T cell activation that leads to chronic inflammation and mucosal damage. A potential role for maladaptation between the intestinal microbiota and the mucosal immune response is suggested by the fact that mutations in the pattern recognition receptor Nod2 are associated with higher risks for developing CD. Although Nod2 deletion in CD4⁺ T cells has been shown to impair the induction of colitis in the murine T cell transfer model, the analysis of T cell intrinsic Nod2 function in T cell differentiation and T cell-mediated immunity is inconsistent between several studies. In addition, the role of T cell intrinsic Nod2 in regulatory T cell (Treg) development and function during colitis remain to be analyzed. In this study, we show that Nod2 expression is higher in activated/memory CD4⁺ T cells and its expression was inducible after T cell receptor (TCR) ligation. Nod2 stimulation with muramyl dipeptide (MDP) led to a nuclear accumulation of c-Rel NF-kB subunit. Although functionally active in CD4⁺ T cells, the deletion of Nod2 did not impair the induction and the prevention of colitis in the T cell transfer model. Moreover, Nod2 deletion did not affect the development of Foxp3⁺ Treg cells in the spleen of recipient mice and Nod2 deficient CD4 T cells expressing the OVA specific transgenic TCR were able to differentiate in Foxp3⁺ Treg cells after OVA feeding. In vitro, CD25⁺ Nod2 deficient T cells suppressed T cell proliferation as well as wild type counter parts and T cell stimulation with MDP did not affect the proliferation and the cytokine secretion of T cells. In conclusion, our data indicate that Nod2 is functional in murine CD4⁺ T cells but its expression is dispensable for the T cell regulation of colitis.     

Canonical and noncanonical inflammasomes in intestinal epithelial cells

Inflammasomes are cytosolic, multimeric protein complexes capable of activating pro‐inflammatory cytokines such as IL‐1β and IL‐18, which play a key role in host defence. Inflammasome components are highly expressed in the intestinal epithelium. In recent years, studies have begun to demonstrate that epithelial‐intrinsic inflammasomes play a critical role in regulating epithelial homeostasis, both by defending the epithelium from pathogenic insult and through the regulation of the mucosal environment. However, the majority of research regarding inflammasome activation has focused on professional immune cells, such as macrophages. Here, we present an overview of the current understanding of inflammasome function in epithelial cells and at mucosal surfaces and, in particular, in the intestine.     

The mitochondrial Nod-like receptor NLRX1 modifies apoptosis through SARM1

Molecular and Cellular Biochemistry - Acrolein is a α-β-unsaturated aldehyde and is toxic to human upon its exposure from the environment. Sources of exposure to acrolein can be from...     

Neuronal differentiation and patterning in Xenopus: the role of cdk5 and a novel activator xp35.2

Cdk5, a member of the cyclin-dependent kinase family, has been shown to play an important role in development of the central nervous system in mammals when partnered by its activator p35. Here we describe the cloning and characterization of a novel activator of cdk5 in Xenopus, Xp35.2. Xp35.2 is expressed during development initially in the earliest differentiating primary neurons in the neural plate and then later in differentiating neural tissue of the brain. This is in contrast to the previously described Xenopus cdk5 activator Xp35.1 which is expressed over the entire expanse of the neural plate in both proliferating and differentiating cells. Expression of both Xp35.1 and Xp35.2 and activation of cdk5 kinase occur when terminal neural differentiation is induced by neurogenin and neuro D overexpression but not when only early stages of neural differentiation are induced by noggin. Moreover, blocking cdk5 kinase activity specifically results in disruption and reduction of the embryonic eye where cdk5 and its Xp35 activators are expressed. Thus, cdk5/p35 complexes function in aspects of neural differentiation and patterning in the early embryo and particularly in formation of the eye.     

p27Xic1, a Cdk inhibitor, promotes the determination of glial cells in Xenopus retina

p27Xic1, a member of the Cip/Kip family of Cdk inhibitors, besides its known function of inhibiting cell division, induces Müller glia from retinoblasts. This novel gliogenic function of p27Xic1 is mediated by part of the N-terminal domain near but distinct from the region that inhibits cyclin-dependent kinases. Cotransfections with dominant-negative and constitutively active Delta and Notch constructs indicate that the gliogenic effects of p27Xic1 work within the context of an active Notch pathway. The gradual increase of p27Xic1 in the developing retina thus not only limits the number of retinal cells but also increasingly favors the fate of the last cell type to be born in the retina, the Müller glia.     

Innate immune recognition of microbes through Nod1 and Nod2: implications for disease

Nod1 and Nod2 are cytosolic proteins involved in intracellular recognition of microbes and their products. Recently, it was shown that these proteins recognize different moieties of bacterial peptidoglycan (PGN) mediating non-specific pathogen resistance and possibly generating signals for the adaptive immune response. Moreover, mutations in the gene encoding Nod2 are associated with increased susceptibility to chronic inflammatory disorders.