Pivotal roles of shear stress in the microenvironmental changes that occur within sentinel lymph nodes

A sentinel lymph node (SLN) is the first lymph node that receives drainage from a primary tumor. According to their physiological and biomechanical characteristics, we hypothesized that SLN contains lymphatic endothelial cells (LEC) that are constantly loaded with high levels of shear stress, which might contribute to the production of a suitable environment for micrometastasis within them. To test this hypothesis, we investigated the effects of shear stress stimulation on the expression of adhesion molecules on human LEC isolated from the lymph vessels nearest the SLN of breast cancers, and on the release of ATP from human LEC. The study clarified that the shear stress stimulation produced a significant increase of ICAM-1 expression at protein and mRNA levels in human LEC. Next, we examined whether the shear stress-mediated increase of ICAM-1 expression accelerates the attachment of carcinoma cells to human LEC. Finally, in in vivo experiments, we evaluated whether exogenous ATP facilitates the expression of carcinoma cell-ligated adhesion molecules in rat SLN. In conclusion, shear stress stimulation induces ICAM-1 expression on human LEC by activating cell surface F1/FO ATP synthase, which might contribute to the development of a premetastatic environment within SLN. (Cancer Sci 2012; 103: 12451252)ArticleCANCER SCIENCE. 103(7):1245-1252 (2012)journal articl

CD38 and its role in oxytocin secretion and social behavior

Here, we review the functional roles of cyclic ADP-ribose and CD38, a transmembrane protein with ADP-ribosyl cyclase activity, in mouse social behavior via the regulation of oxytocin (OXT) release, an essential component of social cognition. Herein we describe data detailing the molecular mechanism of CD38-dependent OXT secretion in CD38 knockout mice. We also review studies that used OXT, OXT receptor (OXTR), or CD38 knockout mice. Additionally, we compare the behavioral impairments that occur in these knockout mice in relation to the OXT system and CD38. This review also examines autism spectrum disorder (ASD), which is characterized by social and communication impairments, in relation to defects in the OXT system. Two single nucleotide polymorphisms (SNPs) in the human CD38 gene are possible risk factors for ASD via inhibition of OXT function. Further analysis of CD38 in relation to the OXT system may provide a better understanding of the neuroendocrinological roles of OXT and CD38 in the hypothalamus and of the pathophysiology of ASD. This article is part of a Special Issue entitled Oxytocin, Vasopressin, and Social Behavior. © 2011 Elsevier Inc

Signal transduction mechanism of interleukin 6 in cultured rat mesangial cells

AbstractInterleukin 6 (IL-6) is one of the potent autocrine growth factors for mesangial cells. We investigated the signal transduction mechanism or IL-6 in cultured rat mesangial cells. IL-6 induced a transient increase of inositol 1,4,5-trisphosphate (Ins 1,4,5-P3) followed by a transient and sustained increase of intracellular calcium concentration, suggesting that IL-6 stimulates phosphoinositide turnover. IL-6 also stimulated prostaglandin E2 (PGE2) production. The IL-6-concentration dependency in PGE2 production was similar to that in Ins 1,4,5-P3 production. We concluded that the action of IL-6 on mesangial cells is exerted at least partially through the enhancement of phosphoinositide turnover and PGE2 production