Involvement of galectin-9 in guinea pig allergic airway inflammation.

Background: There is little information about the involvement of galectin-9 (Gal-9) in allergic inflammation. Thus, we investigated the role of Gal-9 in asthma model guinea pigs.

Methods: Airway resistance (R(aw)) was measured using a double-flow plethysmograph system.

Carbohydrate-recognition domains of galectin-9 are involved in intermolecular interaction with galectin-9 itself and other members of the galectin family.

Galectin-9 (Gal-9) is a tandem-repeat-type member of the galectin family associated with diverse biological processes, such as apoptosis, cell aggregation, and eosinophil chemoattraction. Although the detailed sugar-binding specificity of Gal-9 has been elucidated, molecular mechanisms that underlie these functions remain to be investigated. During the course of our binding study by affinity chromatography and surface plasmon resonance (SPR) analysis, we found that human Gal-9 interacts with immobilized Gal-9 in the protein-protein interaction mode.

Characterization of galectin-9-induced death of Jurkat T cells.

Galectin-9, a mammalian lectin with affinity for beta-galactosides, is known as an apoptosis inducer of activated T lymphocytes. In the present study, we examined the properties of galectin-9-mediated cell death of Jurkat T cells. Galectin-9NC (wild-type), consisting of two CRDs (N-terminal and C-terminal carbohydrate recognition domains), and derivatives of it, galectins-9-NN and -9-CC, induced Jurkat T-cell apoptosis.

[Galectin-9 induces maturation of human monocyte-derived dendritic cells].

We investigated the role of galectin-9 (Gal-9) in maturation of dendritic cells (DC). Culture of immature DCs with exogenous Gal-9 markedly increased the surface expression of CD40, CD54, CD80, CD83, CD86, and HLA-DR in a concentration-dependent manner, although Gal-9 had no effect on differentiation of human monocytes into immature DCs. Gal-9-treated DCs secreted IL-12 but not IL-10, and they elicited the production of Th1 cytokines (IFN-gamma and IL-2), but not that of the Th2 cytokines (IL-4 and IL-5) by allogeneic CD4(+) T cells.

Galectin-9 induces maturation of human monocyte-derived dendritic cells.

Maturation of dendritic cells (DCs) is critical for initiation of immune responses and is regulated by various stimulatory signals. We assessed the role of galectin (Gal)-9 in DC maturation. Culture of immature DCs with exogenous Gal-9 markedly increased the surface expression of CD40, CD54, CD80, CD83, CD86, and HLA-DR in a dose-dependent manner, although Gal-9 had no or little effect on differentiation of human monocytes into immature DCs.

Galectin-9 in physiological and pathological conditions.

We first cloned galectin-9 (Gal-9)/ecalectin as a T cell-derived eosinophil chemoattractant. Gal-9 plays a role in not only accumulation but also activation of eosinophils in experimental allergic models and human allergic patients, because Gal-9 induces eosinophil chemoattraction in vitro and in vivo and activates eosinophils in many aspects. Gal-9 requires divalent galactoside-binding activity but not the linker peptide of Gal-9 to exhibit its biological functions, and an unidentified matrix metalloproteinase is involved in the release of Gal-9.

Hybrid Monte Carlo-diffusion method for light propagation in tissue with a low-scattering region.

The heterogeneity of the tissues in a head, especially the low-scattering cerebrospinal fluid (CSF) layer surrounding the brain has previously been shown to strongly affect light propagation in the brain. The radiosity-diffusion method, in which the light propagation in the CSF layer is assumed to obey the radiosity theory, has been employed to predict the light propagation in head models. Although the CSF layer is assumed to be a nonscattering region in the radiosity-diffusion method, fine arachnoid trabeculae cause faint scattering in the CSF layer in real heads.

Potential roles of galectins in myeloid differentiation into three different lineages.

Little is known about the roles of galectins, a family of beta-galactoside-binding lectins, in myeloid cell differentiation. In the present experiments, we used HL-60 cells as a model of myeloid cell differentiation. The HL-60 cells were differentiated into eosinophil-, monocyte-, and neutrophil-like cells by coculture with sodium butyrate under a mild alkaline condition, phorbol 12-myristate 13-acetate, and dimethyl sulfoxide, respectively.

Galectin-9 induces apoptosis through the calcium-calpain-caspase-1 pathway.

Galectin-9 (Gal-9) induced the apoptosis of not only T cell lines but also of other types of cell lines in a dose- and time-dependent manner. The apoptosis was suppressed by lactose, but not by sucrose, indicating that beta-galactoside binding is essential for Gal-9-induced apoptosis. Moreover, Gal-9 required at least 60 min of Gal-9 binding and possibly de novo protein synthesis to mediate the apoptosis.

Selective eosinophil adhesion to fibroblast via IFN-gamma-induced galectin-9.

Among galectin family members, galectin-9 was first described as a potent eosinophil chemoattractant derived from Ag-stimulated T cells. In the present study a role of galectin-9 in the interaction between eosinophils and fibroblasts was investigated using a human lung fibroblast cell line, HFL-1. RT-PCR, real-time PCR, and Western blot analyses revealed that both galectin-9 mRNA and protein in HFL-1 cells were up-regulated by IFN-gamma stimulation.

Possible role of galectin-9 in cell aggregation and apoptosis of human melanoma cell lines and its clinical significance.

Galectin-9 expression was examined in 6 human melanoma cell lines. Among them, MM-BP proliferated with colony formation, but MM-RU failed. RT-PCR analysis revealed evident expression of galectin-9 mRNA in MM-BP but not in MM-RU.

Association of galectin-9 with eosinophil apoptosis.

Background: There is no information whether galectin-9 (a novel eosinophil chemoattractant) was associated with pathogenesis of eosinophilic disorders.

Methods: We assessed the expression of galectin-9 with imunostaining and in situ hybridization both in the lesion of angiolymphoid hyperplasia with eosinophilia, and peripheral blood eosinophils of eosinophilic patients (E-Eos) in comparison with those of normal volunteers (N-Eos). Regulation of expression of galectin-9 on eosinophils and the effect of galectin-9 on apoptosis of eosinophil were also evaluated.

Regulation of galectin-9 expression and release in Jurkat T cell line cells.

Ecalectin/galectin-9 was recently described as a novel eosinophil chemoattractant highly expressed in immune tissues. We investigated the regulation of galectin-9 expression and release in Jurkat (a T cell line) cells. We demonstrated that medium and long-sized galectin-9 isoforms were constitutively expressed, and phorbol 12-myriastate 13-acetate (PMA) upregulated the level of galectin-9 mRNA in Jurkat cells.

Quantitative analysis of the gastric ulcer healing process using video endoscopic pseudocolor imaging systems.

We developed an endoscopic pseudocolor imaging system in cooperation with Olympus Optical. This system was used for color processing of ulcer images observed over time using an electronic endoscope with measurement capability. The patients were receiving ranitidine (group R) or lansoprazole (group L) for ulcer treatment.

Tissue distribution and molecular heterogeneity of human growth hormone-releasing factor in the transgenic mouse.

Transgenic mice expressing the human growth hormone-releasing factor (hGRF) gene linked to the metallothionein promoter exhibit high circulating levels of hGRF and GH and increased growth. We have described the distribution of GRF immunoreactivity (GRF-IR) in various tissues and characterized its molecular heterogeneity using gel filtration and high performance liquid chromatography (HPLC) and two separate RIAs that recognized mid-molecule and carboxyl-terminal epitopes of hGRF. The highest levels of GRF-IR were in the pituitary, followed by the pancreas.

Growth hormone and prolactin secretion in cultured somatomammotroph cells.

A somatomammotropic cell line (P0) derived from adult rat pituitaries has been maintained in culture for 2 yr. Secretion of GH and PRL by this cell line has been studied in response to hypophysiotropic peptides known to affect the release of both hormones as well as agents that affect second messenger systems in an attempt to characterize the stimulus-secretion mechanisms used by these cells. GH and PRL release during short term (4 h) incubations of P0 cells and primary cultures of dispersed rat pituitary cells was initially measured in response to GRF, TRH, vasoactive intestinal peptide (VIP), and SRIF.

Regulation of growth hormone-releasing hormone gene expression and biosynthesis.

Growth hormone-releasing hormone (GRH) was initially isolated, characterized, sequenced, and cloned from human tumors and subsequently from the hypothalamus of humans and other animal species. Extensive structure-function studies have indicated the amino terminus to be most important for its biologic action, and the primary mechanism of its bioinactivation occurs by cleavage of an amino terminal dipeptide. The GRH gene is expressed primarily in the hypothalamic arcuate nucleus but also in the placenta.

Physiological role of somatostatin-mediated autofeedback regulation for growth hormone: importance of growth hormone in triggering somatostatin release during a trough period of pulsatile growth hormone release in conscious male rats.

In mammals including human, it is generally accepted that growth hormone (GH) can regulate its own secretion through an autofeedback mechanism in which somatostatin (SRIF) may be involved. To explore a physiological role of SRIF-mediated GH autoregulation, the effect of exogenous human GH administration on plasma rat GH response to [D-Ala2, Nle27]-human GH-releasing hormone-(1-28)-agmatine (hGHRH-analog), which does not crossreact with anti-rat GH-releasing hormone gamma-globulin (GHRH-Ab), was examined in conscious male rats treated with GHRH-Ab in the absence and presence of anti-SRIF gamma-globulin (SRIF-Ab). Enhanced SRIF release during a trough period of natural pulsatile GH secretion, suggested by the blunted GH response to exogenous hGHRH-analog, no longer occurred when major GH secretory bursts were abolished by GHRH-Ab treatment.

Discordance between growth hormone (GH) responses after GH-releasing hormone and insulin hypoglycemia in myotonic dystrophy.

Plasma GH responses to human GHRH, arginine, L-dopa, and insulin-induced hypoglycemia were determined in seven myotonic dystrophy (MD) patients. An iv bolus injection of GHRH-(1-44)-NH2 (1 microgram/kg BW) only slightly increased plasma GH concentrations in MD patients. The mean peak plasma GH level after GHRH injection [4.

Calcitonin gene-related peptide-like immunoreactivity in the central nervous system and peripheral organs of rats.

The concentrations of rat calcitonin gene-related peptide-like immunoreactivity (rCGRP-LI) in various organs of male rats as well as the molecular heterogeneity of rCGRP-LI in tissue extracts was examined using a specific radioimmunoassay (RIA) for rCGRP and gel-filtration chromatography. rCGRP-LI was high in extracts of the spinal cord (202 +/- 22.6 pg/mg wet wt.

The effect of hypothalamic deafferentation on rat growth hormone-releasing factor (rGRF)-like immunoreactivity content in the medial basal hypothalamus of rats.

Rat growth hormone releasing factor (rGRF)- and somatostatin (SRIF)-like immunoreactivities (LI) were determined by radioimmunoassay in the medial basal hypothalamus (MBH) of the rat with either complete deafferentation (CD) or a sham operation. Two weeks after the surgery the mean amount of SRIF-LI in the isolated MBH was about 70% less than that in the sham-operated animals. On the other hand, the mean rGRF-LI in the MBH decreased only approximately 30% as compared to the levels in the sham-operated animals, the difference being statistically insignificant.

Effect of oral glucose administration on plasma growth hormone-releasing hormone (GHRH)-like immunoreactivity levels in normal subjects and patients with idiopathic GH deficiency: evidence that GHRH is released not only from the hypothalamus but also from extrahypothalamic tissue.

Using a specific and sensitive RIA for GH-releasing hormone (GHRH), we examined the effect of oral administration of 75 g glucose on peripheral plasma GHRH-like immunoreactivity (GHRH-LI) in normal subjects (n = 12) and patients with idiopathic GH deficiency (IGHD) (n = 6). The normal subjects had two peaks of plasma GHRH-LI after oral glucose administration. The initial peak GHRH-LI levels occurred 30-150 min after glucose ingestion and corresponded to an increase in blood glucose.

Plasma disappearance half-time and metabolic clearance rate of exogenous human growth hormone-releasing hormone-(1-44)-NH2 in normal subjects.

By means of human growth hormone-releasing hormone (hGHRH)-RIA using an antiserum directed toward the C-terminal region of hGHRH-(1-44)-NH2, the plasma disappearance half-time and metabolic clearance rate (MCR) of immuoreactive hGHRH (IR-hGHRH) were examined in normal subjects after an iv bolus injection of synthetic hGHRH-(1-44)-NH2 (1 microgram/kg BW). The disappearance of IR-hGHRH from plasma was characterized by a biexponential decay curve, with initial distribution and subsequent metabolic t1/2 value of 5.0 +/- 1.

Effect of intracerebroventricular administration of rat calcitonin gene-related peptide (CGRP), human calcitonin and [Asu1,7]-eel calcitonin on gastric acid secretion in rats.

The effect of intracerebroventricular injection of rat calcitonin gene-related peptide (CGRP), human calcitonin (CT) and [Asu1,7]-eel CT on the volume and acidity of gastric juice was examined in the pylorus-ligated male rats. These 3 peptides were effective in suppressing both the volume and acidity of secreted gastric juice. Their potency on a molar basis, however, was markedly different; [Asu1,7]-eel CT was most potent, followed by human CT and finally by rat CGRP.

L-dopa stimulates release of hypothalamic growth hormone-releasing hormone in humans.

A sensitive RIA for human GH-releasing hormone-(1-44)-NH2 [hGHRH-(1-44)-NH2] was developed which allows its measurement in human plasma extracts. The assay did not detect hGHRH-(1-37)-OH or hGHRH-(1-40)-OH. A method to extract hGHRH from plasma was developed using silicic acid and acid-acetone, by which recovery of synthetic hGHRH-(1-44)-NH2 from plasma averaged 74.