Intraperitoneal Administration of S100A8 Ameliorates Experimental Acute Colitis in Rats.

S100A8 is a protein that is abundant in neutrophils and macrophages (MΦ), but its role in inflammation remains unclear. This study aimed to assess the immunological role(s) of S100A8 in acute intestinal inflammation in rats and its role in MΦ. Rat recombinant S100A8 (rr-S100A8, 1.

Carbonic Anhydrase III Has Potential as a Biomarker for Experimental Colitis and Functions as an Immune Regulator by Inhibiting Inflammatory Cytokine Secretion.

Ulcerative colitis (UC) is characterized by chronic inflammation of the large intestine, repeated remissions, and symptom relapses. Although unknown components in colonic regions are deeply involved in the pathogenesis of UC, the causes of UC development and aggravation have not yet been elucidated in detail. To identify key factors, we investigated the changes in protein components in the large intestine of rats with dextran sulfate sodium-induced experimental colitis (UCR).

A New Hybrid Protein Is a Novel Regulator for Experimental Colitis in Rats.

We newly developed a hybrid protein, tentatively named rMIKO-1, using gene technology. We herein investigated the effects of rMIKO-1 on activated macrophages and discussed its potential as a suppressor of experimental colitis. Fluorescent microscopy was used to observe the dynamic mobility of rMIKO-1 in macrophages.

Serum complement C3 and α-macroglobulin are potentially useful biomarkers for inflammatory bowel disease patients.

Aims: Ulcerative colitis (UC), characterized by chronic inflammation and its recurrence in the large intestine, is well known as inflammatory bowel disease (IBD). Suitable biomarkers specific for UC are poorly understood till date. We aimed to discover novel serum biomarkers for UC and identify good indicators that reflected the severity of UC.

Circulating S100A8/A9 is potentially a biomarker that could reflect the severity of experimental colitis in rats.

Aims: The clinical significance of circulating S100A8/A9 (calprotectin) in patients with ulcerative colitis (UC) is poorly understood. We examined whether serum S100A8/A9 is a good biomarker for UC, and whether the serum level is a useful index for the severity of the disease.

Main Methods: Experimental animal (rats) were used to verify clinical significance of serum S100A8/A9 as a biomarker.

Serum S100A8/A9 as a Potentially Sensitive Biomarker for Inflammatory Bowel Disease.

Background: The clinical significance of human S100A8/A9 (h-S100A8/A9) in patients with inflammatory bowel disease (IBD) is poorly understood.

Objective: To clarify whether serum S100A8/A9 is a sensitive biomarker for IBD.

Methods: Serum specimens from outpatients with IBD (n = 101) and healthy volunteers (HVs) (n = 101) were used in this study.

Establishment of S100A8 Transgenic Rats to Understand Innate Property of S100A8 and Its Immunological Role.

The innate properties of S100A8 as a regulator in acute inflammation have not yet been elucidated in detail. Our aims are to newly establish S100A8 transgenic rats (Tg-S100A8) and to elucidate the immunological functions of S100A8. Following the treatment with 5% dextran sulfate sodium for 1 week, the body weight in Tg-S100A8 weakly decreased after the start; however, that in Japanese Wistar rats (WT) significantly decreased in the end.

CD68 on rat macrophages binds tightly to S100A8 and S100A9 and helps to regulate the cells' immune functions.

S100A8 and S100A9 (S100 proteins) are regulators of immune cells of myeloid origin. Whereas S100 proteins are found at high concentrations in such cells, their immunologic roles remain unclear. We focused on cluster of differentiation 68 (CD68).

Enzyme-linked immunosorbent assay for S100A9 in the stool of rats with dextran sulfate sodium-induced colitis.

Calprotectin, a heterodimer of S100A8 and S100A9, has been reported to be a useful biomarker in inflammatory bowel disease (IBD); however, the relationship between the fecal level of S100A9 and the extent of inflammation in IBD remains unclear. Our aim was to develop a new enzyme-linked immunosorbent assay (ELISA) for rat S100A9, and to investigate whether changes in fecal S100A9 levels reflect the inflammatory conditions in the intestinal tracts of rats with dextran sulfate sodium (DSS)-induced colitis. Anti-rat S100A9 monoclonal antibodies were raised in mice and used for the development of a novel ELISA for rat S100A9.

Autocrine pathways involving S100A8 and/or S100A9 that are postulated to regulate the immunological functions of macrophages in rats.

The development of ulcerative colitis (UC) is closely associated with abnormally functioning macrophages. Rat S100A8 (r-S100A8) and r-S100A9 (S100 proteins) is abundantly expressed in immune cells of myeloid origin, macrophages; however, it remains unclear why r-S100A9 is dominantly expressed in the macrophages of UC rats (UCR). The purpose of this study was to verify the immunological roles of S100 proteins in UCR.

Clinical usefulness of the PAXgene™ bone marrow RNA system for stabilizing total RNA.

The collection of clinical samples, such as bone marrow (BM) and peripheral blood, is an important procedure for the extraction of the cellular RNA. It is essential to preserve the extracted RNA during and after the collection of clinical samples to ensure the accurate analysis of gene expression. To date, the PAXgene™ Blood RNA System has been proven useful for stabilizing RNA extracted from peripheral blood; however, a problem concerning the stability of the total RNA stored using the system has been identified.

Dynamic mobility of immunological cells expressing S100A8 and S100A9 in vivo: a variety of functional roles of the two proteins as regulators in acute inflammatory reaction.

The immunological properties of rat S100A8 (r-S100A8) and S100A9 (r-S100A9) in immune cells are poorly understood. Enzyme-linked immunosorbent assay (ELISA) for r-S100A9 enabled us to discuss the differential functional roles of the two proteins, and their localization in the cells was observed microscopically. Recombinant human S100A8 (rh-S100A8) or S100A9 (rh-S100A9) were intravenously administrated into rats with LPS-induced liver damage.

S100A8/A9 complex as a new biomarker in prediction of mortality in elderly patients with severe heart failure.

Background: S100A8/A9 complex is a new inflammation-related protein and has a positive correlation with C-reaction protein level. However its role in chronic heart failure (CHF) remains unclear.

Methods And Results: Circulating levels of S100A8/A9 complex and other biomarkers (IL-6, IL-8, TNF-α, and BNP) were measured in CHF (n = 54) and hypertensive without CHF (n = 31) as well as healthy subjects (n = 23), with follow up to 1480 days.

[Possible mechanism for regulation of inflammatory responses with the S100A8/A9 protein].

We have described a possible mechanism for the regulation of excessive inflammatory responses with S100A8/A9 protein in damaged rat livers. Recombinant human S100A8(r-S100A8) and S100A9 (r-S100A9) were expressed in E. coli cells, and their heterodimer (r-S100A8/A9) with 90% approximate purity was also prepared successfully.

Identification of serum proteins that bind with S100A8, S100A9 and S100A8/A9: clinical significance of using proteins for monitoring the postoperative condition of liver recipients.

Background: Serum proteins that non-specifically bind with human S100A8/A9 (h-S100A8/A9) have been proposed. Our aim was to isolate and identify these proteins, and verify their clinical significance for monitoring the postoperative condition of liver recipients, and further to discuss the transportation of human fibronectin (h-FN) with h-S100A8/A9 and its functional role in vivo.

Methods: To isolate the serum proteins, recombinant human S100A8, S100A9 and S100A8/A9 affinity columns were used.

Enhanced expression of the S100A8/A9 complex in acute myocardial infarction patients.

Background: S100A8/A9 complex (S100A8/A9) is expressed in activated human neutrophils and macrophages. Enhanced expression of S100A8/A9 in atherosclerotic plaque of patients with unstable angina pectoris (UAP) has been demonstrated, but its profile in acute myocardial infarction (AMI) has not been clarified.

Methods And Results: Serum S100A8/A9 levels were serially measured in patients with AMI (n=55) and UAP (n=16) during the acute period.

Serum ornithine carbamyltransferase reflects hepatic damage in diabetic obese mice.

Background And Aim: As ornithine carbamyltransferase (OCT) has proved to be a sensitive serum marker in the detection of hepatotoxicity in several models, it is important to confirm its application to the diagnosis of non-alcoholic fatty liver disease.

Methods: C57BL/6, KK-Ta and KK-Ay mice were fed a high-fat diet for 8 weeks and serum enzyme markers were examined. Serum OCT and alanine aminotransferase (ALT) were also measured in diabetic obese ob/ob and db/db mice fed a normal diet.

[Possibility of formation of the S100A8/A9-proinflammatory cytokine complexes in vivo in acute inflammation and their functional roles].

We previously hypothesized that S100A8/A9 binds with several kinds of proinflammatory cytokines, such as TNF-alpha, IL-6 and IL-1beta, to form the S100A8/A9-proinflammatory cytokine complexes in vivo in acute inflammation, leading to subsidence of inflammatory responses. Our goal was to verify the presence of these complexes in liver tissues of rats with lipopolysaccharide (LPS) induced damage. We firstly prepared two kinds of the full-length cDNA encoding amino acid sequences of human S100A8 and S100A9 proteins, and constructed their pCold-I expression vectors.

Suppression of inflammation in rat autoimmune myocarditis by S100A8/A9 through modulation of the proinflammatory cytokine network.

Aims: S100A8/A9 is expressed in activated monocytes/macrophages and assumed to be heavily involved in the pathogenesis of acute inflammation. Although several studies have asserted that S100A8/A9 has a proinflammatory function, the exact biological function of S100A8/A9 is yet to be described. We examined the anti-inflammatory effects of S100A8/A9 on experimental autoimmune myocarditis (EAM) in rats.

Ornithine carbamyltransferase is a sensitive marker for alcohol-induced liver injury.

Background: Although mitochondrion-derived markers such as ornithine carbamyltransferase (OCT) and glutamate dehydrogenase (GLDH) have been reported to be good markers for alcohol-induced hepatic injury, their use has been limited due to the notion that mitochondrial markers are less sensitive than cytosol-derived markers. We determined the clinical importance of mitochondrion-derived markers in the evaluation of alcohol-induced hepatotoxicity.

Methods: Rats were administered alcohol chronically (5-30% ethanol in drinking water with or without high fat diet feeding for 15 weeks) and hepatic damages were evaluated by serum OCT and GLDH, together with other liver enzymes such as alanine aminotransferase and aspartate aminotransferase.

Marked elevation of serum mitochondrion-derived markers in mild models of non-alcoholic steatohepatitis in rats.

Background And Aim: In order to find sensitive serum markers in non-alcoholic steatohepatitis, liver-specific injury markers were thoroughly examined in mild models of NASH in rats.

Methods: Wistar and Sprague-Dawley rats were fed a choline-deficient diet for 4 weeks, and serum activities of liver-specific enzyme markers were examined. In the drug-induced steatohepatitis model, tetracycline (0.

Superiority of serum type-I arginase and ornithine carbamyltransferase in the detection of toxicant-induced acute hepatic injury in rats.

Background: Despite the restricted distribution to mitochondria of hepatocytes in the periportal region, ornithine carbamyltransferase (OCT) have been suggested to be a sensitive marker in addition to type-I arginase (ARG), even in centrilobular damage of the liver. We attempted to confirm the universal advantages of ARG and OCT in the evaluation of hepatotoxicity induced by toxicants, and to clarify whether the character of a marker is a more important factor than its localization in its clinical superiority.

Methods: Rats were administered carbon tetrachloride, allyl alcohol, D-galactosamine, lipopolysaccharide, and concanavalin A and the course of damage was monitored by serum ARG and OCT, together with alanine aminotransferase (ALT) and aspartate aminotransferase (AST).

A case with transient increases in serum S100A8/A9 levels implying acute inflammatory responses after pancreatic islet transplantation.

We investigated a patient with type 1 diabetes mellitus undergoing pancreatic islets transplantation. In this patient, we evaluated the clinical usefulness of serial measurement of serum S100A8/A9 complex levels for detecting acute inflammatory responses associated with rejection of transplanted pancreatic islets. The serum S100A8/A9 complex was a more sensitive marker for acute inflammation associated with islet transplant rejection than the serum C-reactive protein.

Dose-dependency in pleiotropic effects of atorvastatin.

Statins are recognized as the principal and most effective class of drugs for reducing serum cholesterol levels and, therefore, significantly reducing cardiovascular events and mortality. Statins may have a wide range of beneficial biological effects in addition to lipid lowering, a phenomenon commonly termed a 'pleiotropic effect'. However, the dose-dependency of these effects remains unclear.