Biomedical subjects

Shiro Watanabe

Publications and source records attributed to Shiro Watanabe.

At least 19 recordsLinked to original sources

PubMed2006

Role of IP-10/CXCL10 in the progression of pancreatitis-like injury in mice after murine retroviral infection.

Exocrinopathy and pancreatitis-like injury were developed in C57BL/6 (B6) mice infected with LP-BM5 murine leukemia virus, which is known to induce murine acquired immunodeficiency syndrome (MAIDS). The role of chemokines, especially CXCL10/interferon (IFN)-gamma-inducible protein 10 (IP-10), a chemokine to attract CXCR3+ T helper 1-type CD4+ T cells, has not been investigated thoroughly in the pathogenesis of pancreatitis. B6 mice were inoculated intraperitoneally with LP-BM5 and then injected every week with either an antibody against IP-10 or a control antibody. Eight weeks after infection, we analyzed the effect of IP-10 neutralization. Anti-IP-10 antibody treatment did not change the generalized lymphadenopathy and hepatosplenomegaly of mice with MAIDS. The treatment significantly reduced the number of IP-10- and CXCR3-positive cells in the mesenteric lymph nodes (mLNs) but not the phenotypes and gross numbers of cells. In contrast, IP-10 neutralization reduced the number of mononuclear cells infiltrating into the pancreas. Anti-IP-10 antibody treatment did not change the numbers of IFN-gamma+ and IL10+ cells in the mLN but significantly reduced their numbers, especially IFN-gamma+ and IL-10+ CD4+ T cells and IFN-gamma+ Mac-1+ cells, in the pancreas. IP-10 neutralization ameliorated the pancreatic lesions of mice with MAIDS probably by blocking the cellular infiltration of CD4+ T cells and IFN-gamma+ Mac-1+ cells into the pancreas at least at 8 wk after infection, suggesting that IP-10 and these cells might play a key role in the development of chronic autoimmune pancreatitis.

Animals↗

PubMed2006

Differential effects of selective cyclooxygenase (COX)-1 and COX-2 inhibitors on anorexic response and prostaglandin generation in various tissues induced by zymosan.

We have shown that anorexic response is induced by intraperitoneal injection of zymosan in mice, although the role of prostaglandins in this response is relatively unknown as compared with lipopolysaccharide (LPS)-induced anorexic response. Indomethacin (0.5 and 2.0 mg/kg), a non-selective cyclooxygenase (COX) inhibitor, as well as meloxicam (0.5 mg/kg), a selective COX-2 inhibitor, but not FR122047 (2.0 mg/kg), a selective COX-1 inhibitor, attenuated zymosan-induced anorexia. Zymosan injection elevated COX-2 expression in brain and liver but not in small intestine and colon. Meloxicam (0.5 mg/kg) and FR122047 treatment (2.0 mg/kg) similarly suppressed the generation of brain prostaglandin E(2) (PGE(2)) and peritoneal prostacyclin (PGI(2)) upon zymosan injection. PGE(2) generation in liver upon zymosan injection was suppressed by meloxicam (0.5 mg/kg) but not by FR122047 treatment (2.0 mg/kg). Our observations suggest that COX-2 plays an important role in zymosan-induced anorexia, which is a similar feature in LPS-induced anorexic response. However, non-selective inhibition by selective COX-1 and COX-2 inhibitors of brain PGE(2) generation upon zymosan injection does not support the role of COX-2 expressed in brain in zymosan-induced anorexic response. PGE(2) generation in liver may account for peripheral role of COX-2 in zymosan-induced anorexic response.

Animals↗

PubMed2005

Baicalein 5,6,7-trimethyl ether, a flavonoid derivative, stimulates fatty acid beta-oxidation in skin fibroblasts of X-linked adrenoleukodystrophy.

The purpose of the present study is to identify bioactive compounds with potential for X-linked adrenoleukodystrophy (X-ALD) pharmacological therapy. Various plant natural products including flavonoids were tested for their ability to ameliorate the abnormality of very long chain fatty acid (VLCFA) metabolism in cultured skin-fibroblasts from X-ALD patients. Of the compounds tested, baicalein 5,6,7-trimethyl ether (baicalein-tri-Me) was found to significantly stimulate the VLCFA beta-oxidation activity. Furthermore, the incorporation of [1-(14)C]lignoceric acid into cholesteryl esters was markedly reduced towards the normal level and the VLCFA (C24:0 and C26:0) content was decreased. These results make baicalein-tri-Me a candidate for the therapeutic compound for X-ALD.

Adrenoleukodystrophy↗

PubMed2005

The effect of fish oil on physical aggression in schoolchildren--a randomized, double-blind, placebo-controlled trial.

OBJECTIVES: The aim of the study was to investigate whether fish oil supplementation affected Japanese schoolchildren's behavior, with changes in aggression over time as the primary endpoint. DESIGN AND SUBJECTS: A placebo-controlled double-blind study with 166 schoolchildren 9-12 years of age was performed. The subjects of the fish oil group (n=83) took fish oil-fortified foods (bread, sausage and spaghetti). These foods were provided in amounts such that each subject in the fish oil group had an intake of 3600 mg of docosahexaenoic acid+840 mg of eicosapentaenoic acid (EPA)/week for 3 months. The rest (the controls, n=83) took control supplements. At the start and end of the study, psychological tests were performed to assess their aggression. RESULTS: Physical aggression assessed by Hostility-Aggression Questionnaire for Children in girls increased significantly (median: 13 to 15, n=42) in the control group and did not change (13 to 13, n=43) in the fish oil group with a significant intergroup difference (P=.008) with baseline as covariate. The changes in physical aggression scores over time and those of the ratio of EPA/arachidonic acid in RBC (DeltaEPA/AA) were significantly correlated in girls who agreed to blood collection (r=-.53, P=.01, n=23). On the contrary, there were no significant changes in physical aggression in boys. Aggression against others (extraggression) assessed by Picture Frustration Study did not change in the control group (median: 5 to 5) but increased significantly in the fish oil group (4 to 5) with a significant intergroup difference (P=.02) with baseline as covariate. These changes in extraggression might be explained partly by significantly lower baseline values of extraggression in the fish oil group (P=.02) than in the control group. There were no significant correlations between Deltaextraggression and DeltaEPA/AA in blood-sampled children (n=49). Impulsivity of girls assessed by parents/guardians using the diagnostic criteria for attention deficit/hyperactivity disorder of DSM-IV was reduced in the fish oil group (1 to 0) with a significant (P=.008) intergroup difference from the control group (1 to 1). There were no significant correlations between Deltaimpulsivity and DeltaEPA/AA in blood-sampled girls. In males, impulsivity reduced in both groups without any intergroup differences. CONCLUSION: There is a possibility that changes in fatty acid nutrition might affect physical aggression especially in girls.

Aggression↗

PubMed2005

Effect of omega-3 fatty acid-containing phospholipids on blood catecholamine concentrations in healthy volunteers: a randomized, placebo-controlled, double-blind trial.

OBJECTIVE: We previously reported that administration of fish oil rich in docosahexaenoic acid (DHA) increased the plasma ratio of epinephrine to norepinephrine (NE) at rest in young adults who were under chronic stress and that this effect was achieved mainly through depression of NE. However, not many reports have documented the effects of eicosapentaenoic acid (EPA) and DHA on blood catecholamine levels in healthy humans. Therefore, we performed another intervention study to test their effect on catecholamines with healthy subjects under no chronic stress. METHODS: Twenty-one healthy young adults (15 men and 6 women) were randomly assigned to an omega-3 group (n = 9) or a control group (n = 12) in a double-blind manner. Twenty capsules of shellfish-derived lipids containing 762 mg of EPA plus DHA per day were administered to the omega-3 group for 2 mo. The controls took the same amount of placebo capsules. Fasting blood samples after a 30-min rest with a catheter in a forearm vein were obtained at the start and the end of the study for catecholamine measurements. RESULTS: EPA but not DHA concentrations in red blood cells significantly increased in the omega-3 group compared with the control group (P < 0.001). Plasma NE concentrations were significantly decreased in the omega-3 group (from 1.49 +/- 0.39 nmol/L to 1.05 +/- 0.14 nmol/L) compared with the control group (from 1.12 +/- 0.24 nmol/L to 1.39 +/- 0.32 nmol/L) with analysis of covariance (P < 0.001). The differences remained significant (P = 0.01) even after deletion of three subjects in the omega-3 group who had the highest baseline NE values and one in the control group who had the lowest baseline NE value to nullify a significant baseline differences in NE between groups. CONCLUSION: This study demonstrated that EPA plus DHA supplementation lowered plasma NE concentrations in normal volunteers even at the small dose of 762 mg of EPA plus DHA per day. This effect of EPA plus DHA to lower plasma NE concentrations may be important to understand some of the effects of fish oils on diseases.

Adolescent↗

PubMed2005

Adult Henoch-Schönlein purpura with severe abdominal pain treated with dapsone and factor XIII concentrate.

We describe an adult patient with Henoch-Schönlein purpura who had arthralgia, severe abdominal pain, and low plasma factor XIII activity. Corticosteroids were not used because of his history of multidrug-resistant pulmonary tuberculosis. Dapsone had no immediate effect on his abdominal pain, but appeared to have some effect on the purpura and arthralgia. Marked improvement of the abdominal pain was observed immediately after the administration of factor XIII concentrate. Factor XIII concentrate may be useful for alleviating abdominal pain in Henoch-Schönlein purpura patients when corticosteroids are contraindicated

Abdominal Pain↗

PubMed2005

Dietary supplementation with n-3 polyunsaturated fatty acids attenuates the depression of food-motivated behavior during zymosan-induced peritonitis.

Peripheral inflammation is accompanied by neurobehavioral alterations such as depression of feeding, exploratory and sexual behaviors. Our previous investigation reported that dietary enrichment with n-3 polyunsaturated fatty acids (PUFA) attenuated the depression of food-motivated behavior and social exploration, but not endocrinological and metabolic disturbances in the mice with systemic inflammation induced by lipopolysaccharide (LPS). We here demonstrate that dietary n-3 PUFA also attenuate the reduction of food-motivated behavior during zymosan-induced peritonitis in mice without influencing plasma leakage into peritoneum and writhing response. Our results suggest that the common mechanism is involved in the attenuation of behavioral depression during systemic and local inflammation by dietary n-3 PUFA.

Animals↗

PubMed2004

Suicide attempt and n-3 fatty acid levels in red blood cells: a case control study in China.

BACKGROUND: Epidemiologic studies show that low fish intake is a risk factor of suicidality; however, there are no case-control studies investigating suicide attempt risk and tissue n-3 fatty acid levels. METHODS: We recruited 100 suicide-attempt cases and another 100 control patients injured by accidents who were admitted to three hospitals affiliated with Dalian Medical University in Dalian, China. Case and control subjects were matched for age, gender, and smoking status. Those who were inebriated at the time of hospitalization were excluded. Blood was sampled immediately after admission to a hospital. Washed red blood cells (RBCs) were obtained, and the fatty acid composition of the total RBC phospholipid fraction was analyzed by gas chromatography. RESULTS: Eicosapentaenoic acid (EPA) levels in RBC in the case subjects were significantly lower than those of the control subjects (.74 +/-.52% vs. 1.06 +/-.62%, p <.0001). When the highest and lowest quartiles of EPA in RBC were compared, the odds ratios of suicide attempt was.12 in the highest quartile (95% confidence interval:.04-.36, p for trend =.0001) after adjustment for possible confounding factors CONCLUSIONS: Our findings suggest that low n-3 fatty acid levels in tissues were a risk factor of suicide attempt. Further studies including intervention with fish oil are warranted.

Adult↗

PubMed2004

Pressure activates rat pancreatic stellate cells.

Pancreatic stellate cells (PSCs) play a central role in development of pancreatic fibrosis. In chronic pancreatitis, pancreatic tissue pressure is higher than that of the normal pancreas. We here evaluate the effects of pressure on the activation of rat PSCs. PSCs were isolated from the pancreas of Wistar rat using collagenase digestion and centrifugation with Nycodenz gradient. Pressure was applied to cultured rat PSCs by adding compressed helium gas into the pressure-loading apparatus to raise the internal pressure. Cell proliferation rate was assessed by 5-bromo-2'-deoxyuridine (BrdU) incorporation. MAPK protein levels and alpha-smooth muscle actin (alpha-SMA) expression were evaluated by Western blot analysis. Concentration of activated transforming growth factor-beta1 (TGF-beta1) secreted from PSCs into culture medium was determined by ELISA. Collagen type I mRNA expression and collagen secretion were assessed by quantitative PCR and Sirius red dye binding assay, respectively. Application of pressure significantly increased BrdU incorporation and alpha-SMA expression. In addition, pressure rapidly increased the phosphorylation of p44/42 and p38 MAPK. Treatment of PSCs with an MEK inhibitor and p38 MAPK inhibitor suppressed pressure-induced cell proliferation and alpha-SMA expression, respectively. Moreover, pressure significantly promoted activated TGF-beta1 secretion, collagen type I mRNA expression, and collagen secretion. Our results demonstrate that pressure itself activates rat PSCs and suggest that increased pancreatic tissue pressure may accelerate the development of pancreatic fibrosis in chronic pancreatitis.

Actins↗

PubMed2004

Angiotensin II type 1 receptor interaction is an important regulator for the development of pancreatic fibrosis in mice.

The renin-angiotensin system (RAS) plays important roles in various pathophysiological processes. However, the role of the RAS in pancreatic fibrosis has not been established. We investigated the role of angiotensin II (ANG II)-ANG II type 1 (AT(1)) receptor pathway in the development of pancreatic fibrosis with AT(1a) receptor-deficient [AT(1a)(-/-)] mice. To induce pancreatic fibrosis, AT(1a)(-/-) and wild-type (WT) mice were submitted to three episodes of acute pancreatitis induced by six intraperitoneal injections of 50 microg/kg body wt cerulein at hourly intervals, per week, for four consecutive weeks. Pancreatic fibrosis was assessed by histology and hydroxyproline content. Pancreatic stellate cell (PSC) activation and the localization of AT(1) receptors were assessed by Western blot analysis for alpha-smooth muscle actin and immunostaining. Transforming growth factor-beta(1) (TGF-beta(1)) mRNA expression in the pancreas was assessed by RT-PCR. Six intraperitoneal injections of cerulein induced acute pancreatitis in both AT(1a)(-/-) and WT mice. There were no significant differences between two groups with regard to serum amylase and histological changes. Pancreatic fibrosis induced by repeated episodes of acute pancreatitis was significantly attenuated in AT(1a)(-/-) mice compared with that in WT mice. This finding was accompanied by a reduction of activated PSCs. Dual-immunofluorescence staining in WT mice revealed that activated PSCs express AT(1) receptors. The level of TGF-beta(1) mRNA was lower in AT(1a)(-/-) mice than in WT mice. Our results demonstrate that the ANG II-AT(1) receptor pathway is not essential for the local pancreatic injury in acute pancreatitis but plays an important role in the development of pancreatic fibrosis through PSC activation and proliferation.

Animals↗

PubMed2004

Dietary n-3 fatty acids selectively attenuate LPS-induced behavioral depression in mice.

Systemic administration of bacterial lipopolysaccharide (LPS) induces a series of physiological and pathological alterations as well as behavioral depression in experimental animals. These alterations induced by LPS administration are known to be mediated by endogenous cytokines and arachidonate metabolites, which may be modulated by dietary n-3 fatty acids. Mice were fed a diet supplemented with n-3 or n-6 fatty acids for 4 weeks prior to LPS administration. Food-motivated behavior after intraperitoneal administration of LPS as compared with that before LPS administration was significantly depressed in the mice fed with the n-6 fatty-acid-rich diet (47% to 85% reduction; P<.05) but not significantly in the mice fed with the n-3 fatty-acid-rich diet. Depression of social exploration by intraperitoneal LPS administration in the n-3 fatty-acid-rich diet group (39% reduction vs. vehicle group) was significantly less in the n-6 fatty-acid-rich diet group (76% reduction vs. vehicle group; P<.05). The behavioral depressions induced by intracerebroventricular LPS injection were not significantly different between the two dietary groups (P=.60). The elevation of serum corticosterone and the hypoglycemic response following intraperitoneal LPS administration were not significantly different between the two dietary groups (P=.57 and P=.43, respectively). We demonstrate that dietary n-3 fatty acids attenuate behavioral depression in mice peripherally administered with LPS without affecting the increase in serum corticosterone and the decrease in serum glucose concentration.

Analysis of Variance↗

PubMed2004

Inhibition of transforming growth factor beta decreases pancreatic fibrosis and protects the pancreas against chronic injury in mice.

Transforming growth factor-beta (TGF-beta) is an important cytokine in the fibrogenesis in many organs, including the pancreas. Using an adenoviral vector expressing the entire extracellular domain of type II human TGF-beta receptor (AdTbeta-ExR), we investigated whether inhibition of TGF-beta action is effective against persistent pancreatic fibrosis, and whether it exerts a beneficial effect on the pancreas in the process of chronic injury. To induce chronic pancreatic injury and pancreatic fibrosis, mice were subjected to three episodes of acute pancreatitis induced by six intraperitoneal injections of 50 microg/kg body weight cerulein at hourly intervals, per week for 3 consecutive weeks. Mice were infected once with AdTbeta-ExR, or with a control adenoviral vector expressing bacterial beta-galactosidase (AdLacZ). Pancreatic fibrosis was evaluated by histology and hydroxyproline content. Activation of pancreatic stellate cells (PSCs) was assessed by immunostaining for alpha-smooth muscle actin. Apoptosis and proliferation of acinar cells were assessed by immunostaining of ssDNA and Ki-67, respectively. Three-week cerulein injection induced pancreatic fibrosis and pancreatic atrophy with proliferation of activated PSCs. In AdTbeta-ExR-injected mice, but not AdLacZ-injected mice, pancreatic fibrosis was significantly attenuated. This finding was accompanied by a reduction of activated PSCs. AdTbeta-ExR, but not AdLacZ, significantly increased pancreas weight after chronic pancreatic injury. AdTbeta-ExR did not change the proportion of proliferating acinar cells, whereas it reduced the number of apoptotic acinar cells. Our results demonstrate that inhibition of TGF-beta action not only decreases pancreatic fibrosis but also protects the pancreas against chronic injury by preventing acinar cell apoptosis.

Animals↗

PubMed2004

Effect of dietary enrichment with n-3 polyunsaturated fatty acids (PUFA) or n-9 PUFA on arachidonate metabolism in vivo and experimentally induced inflammation in mice.

Mice were fed a diet supplemented with palm oil (control diet), n-3 polyunsaturated fatty acids (PUFA)-, or n-9 PUFA-rich oil for 3 weeks. The n-3 PUFA-rich diet suppressed the generation of both leukotrienes (LT) and prostaglandins (PG), but the n-9 PUFA-rich diet did LT but not PG generation during acute inflammation. Leukocyte accumulation during acute inflammation was not different in the n-3 or n-9 PUFA-rich diet group as compared with the control group. The n-3 PUFA-rich diet but not the n-9 PUFA-rich diet suppressed Freund's adjuvant-induced granuloma formation. The n-9 PUFA-rich diet significantly attenuated galactosamine/lipopolysaccharide-induced liver injury more effectively than the n-3 PUFA-rich diet as compared with the control diet. The present study revealed the differential modification of experimentally induced inflammation in mice by dietary n-3 PUFA and n-9 PUFA, which may be due to their different effects on 5-lipoxygenease and cyclooxygenase metabolism of arachidonic acid during inflammatory processes.

Acute Disease↗

PubMed2003

n-3 long-chain FA decrease serum levels of TG and remnant-like particle-cholesterol in humans.

A large number of papers have reported that administration of n-3 FA reduced serum TG concentrations in hypertriglyceridemic patients. However, few studies have examined the effect of n-3 FA on serum concentrations of remnant-like particle (RLP) cholesterol. Volunteers (n = 41) whose serum TG concentrations were 100-300 mg/dL were recruited and randomly assigned to either an n-3 FA group or a control group with stratification by sex, age, and serum TG level in a double-blind manner. The subjects in the n-3 FA group were administered 125 mL of fermented soybean milk with fish oil containing 600 mg of EPA and 260 mg of DHA/d for 12 wk. The controls consumed control soybean milk with olive oil. Fasting blood samples were obtained before the start of administration and at 4, 8, and 12 wk. EPA concentrations in red blood cells increased significantly in all but one subject in the n-3 FA group, with no significant changes in the control group. TG levels decreased more in the n-3 FA group than in the control group at weeks 4 (P < 0.05), 8 (P < 0.01), and 12 (P < 0.05) with their baseline as covariate. RLP cholesterol levels decreased more in the n-3 FA group than in the control at weeks 8 (P < 0.01) and 12 (P < 0.05) with their baseline as covariate. The groups did not differ in the other lipid levels. It is likely that n-3 long-chain FA may exert anti-atherosclerotic effects by lowering serum TG and RLP-cholesterol levels even at the dose of 860 mg/d.

Adult↗

PubMed2003

Kinetic analysis of the development of pancreatic lesions in mice infected with a murine retrovirus.

Sjögren's syndrome (SjS)-like sialoadenitis and exocrine pancreatitis were induced in mice infected with LP-BM5 murine leukemia virus, which induces a severe immunodeficiency termed murine AIDS (MAIDS). All mice with MAIDS showed advancing cellular infiltration around the pancreatic ducts as well as systemic exocrinopathy. The primary target tissue of the pancreas was acinar cells, and the pancreatic islets were well preserved until a late phase of the disease. Immunofluorescence and flow cytometry demonstrated that CD4(+) T cells, Mac-1(+) cells, and B220(+) cells were major inflammatory components, and IFN-gamma and IL-10 were mainly detected on CD4(+) T and Mac-1(+) cells in the pancreas. Both Th1 and Th2 cells were found. TUNEL(+) apoptotic cells were mostly detected among pancreas-infiltrating cells. Fas ligand and TNF-alpha were also detected among pancreas-infiltrating cells, whereas Fas was rarely expressed in the pancreatic acinar cells. Thus, MAIDS mice could be valuable for analyzing the pathogenesis of autoimmune-related pancreatitis associated with SjS.

Animals↗

PubMed2003

A novel rat lipoxin A4 receptor that is conserved in structure and function.

1. Lipoxin (LX) A(4) and aspirin-triggered-LX (ATL) are endogenous lipid-derived mediators that regulate leukocyte trafficking via specific LXA(4) receptors (ALX), and are involved in endogenous anti-inflammation and resolution. Both LXA(4) and ATL are produced by rat tissues in vitro as well as in vivo. In rats, LXA(4) and ATL exhibit potent physiological and pathophysiological roles. Thus, we set out to determine whether ALX is expressed in rat tissues and its potential role in modulating leukocyte trafficking with LXA(4) and ATL. 2. In rats, a stable analog of ATL, when given intravenously with two consecutive doses at approximately 60 microg kg(-1) each injection, significantly inhibited neutrophil infiltration (approximately 43%) and protein extravasation (approximately 42%) in a casein-induced peritonitis. 3. The rat orthologue of ALX was cloned from peripheral blood leukocytes encoding a putative G protein-coupled receptor (GPCR). It gave approximately 74 and approximately 84% homology, respectively to the deduced amino-acid sequences of the human and mouse ALX. 4. Tissue distribution analysis by RNase protection revealed that this rat receptor is expressed in tissues/cells, where LXA(4) displays physiological and pathophysiological roles, namely, lung, kidney and leukocytes. 5. The rat orthologue of ALX gave specific radioligand binding with [(3)H]LXA(4) and [(125)-Tyr]-annexin 1-derived peptide with apparent K(d) values of 5 and 820 nM, respectively, that are at levels comparable to those of the human ALX. 6. Activation of rat ALX inhibited tumor necrosis factor alpha-mediated nuclear factor kappaB activity in a ligand-dependent manner utilizing a luciferase reporter gene system. 7. Together, these results are the first demonstration of a rat ALX that is conserved in both structure and function suggesting that ALX plays key roles in regulating effector immune responses from murine to human species.

Amino Acid Sequence↗

PubMed2003

Cholesterol synthesis in mice is suppressed but lipofuscin formation is not affected by long-term feeding of n-3 fatty acid-enriched oils compared with lard and n-6 fatty acid-enriched oils.

Hypocholesterolemic activity of dietary polyunsaturated fatty acids is observed after relatively short-term but not long-term feedings, and their long-term feedings are suspected to accelerate aging through tissue accumulation of lipid peroxides and age pigments (lipofuscin). To define the long-term effects of fats and oils in more detail, female mice were fed a conventional basal diet supplemented with lard (Lar), high-linoleic (n-6) safflower oil (Saf), rapeseed oil (Rap), high-alpha-linolenic (n-3) perilla oil (Per), or a mixture of ethyl docosahexaenoate and soybean oil (DHA/Soy) from 17 weeks to 71 weeks of age. The DHA/Soy and Per groups had decreased serum cholesterol levels compared with the Lar and Saf groups, but the difference between the Lar and Saf groups was not significant. The 3-hydroxy-3-methyglutary-CoA (HMG-CoA) reductase activity in the liver was also significantly lower in the Per and DHA/Soy groups. However, no significant difference in lipofuscin contents in the brain and liver was observed among the 5 dietary groups, despite significant differences in peroxidizability indices of the dietary and/or tissue lipids. These results indicate that n-3 fatty acid-rich oils are hypocholesterolemic by suppressing hepatic HMG-CoA reductase activity compared with animal fats and high-linoleic (n-6) oil, but tissue lipofuscin contents are not affected by a long-term feeding of fats and oils with different degree of unsaturation in mice.

Acyl Coenzyme A↗

PubMed2002

Blockade of CXCL10 protects mice from acute colitis and enhances crypt cell survival.

Crypt cell renewal is essential for normal intestinal homeostasis as well as mucosal regeneration following injury. However, the factors regulating crypt cell growth in pathological conditions are not fully understood. We report here that the endogenously produced chemokine CXCL10 regulates crypt cell proliferation. CXCL10 was constitutively expressed by basal crypts in mouse colon, but the expression of CXCL10 as well as CXCR3 was enhanced in the epithelium in the proliferative zone after oral administration of dextran sulfate sodium. Neutralization of CXCL10 protected mice from epithelial ulceration by promoting crypt cell survival without evidence of altered immune cell infiltration. Furthermore, recombinant CXCL10 administration into mice inhibited intestinal epithelial cell proliferation. These findings suggest that CXCL10 regulates crypt cell growth to maintain intestinal homeostasis in an autocrine or paracrine fashion. Thus, CXCL10 can be a new therapeutic target for inflammatory bowel disease by controlling the dynamics of epithelial homeostasis.

Acute Disease↗