Expression of genes encoding interleukin 15 and its receptor subunits in the duodenal and colonic mucosae of dogs with chronic enteropathy.

A pro-inflammatory role of interleukin (IL)-15 and IL-15 receptor (R) in chronic intestinal inflammation, such as inflammatory bowel disease, has been reported in humans. However, the contribution of IL-15 signaling in the pathogenesis of canine chronic enteropathy (CE) remains unclear. Therefore, as a first step in elucidating the importance of IL-15 signaling in canine CE, we measured the mRNA expression of IL-15 and IL-15R subunits, including IL-15Rα, IL-15Rß, and IL-15Rγ, in the duodenal and colonic mucosae of healthy dogs and those with CE, including food-responsive enteropathy (FRE), antibiotic-responsive enteropathy (ARE), and immunosuppressant-responsive enteropathy (IRE). Real-time PCR analysis revealed significantly lower IL-15Rα mRNA expression levels in the duodenal mucosa of dogs with IRE compared to healthy dogs. In contrast, the mRNA expression levels of IL-15, IL-15Rß, and IL-15Rγ in the duodenal mucosa and IL-15, IL-15Rα, IL-15Rß, and IL-15Rγ in the colonic mucosa did not differ among healthy dogs and those with FRE, ARE, or IRE. These findings suggest that decreased mRNA expression of IL-15Rα might be involved in the pathogenesis of duodenitis in dogs with IRE. Moreover, even in canine CE, IL-15 signaling appears to play different roles in duodenitis and colitis in dogs with FRE, ARE, and IRE. However, there were no correlations between the gene expression levels of IL-15Rα and clinical severity or histopathological scores in the duodenum of dogs with IRE. Further studies are necessary to investigate the IL-15Rα protein localization and to determine how impaired IL-15Rα expression contributes to the development of duodenitis in dogs with IRE.

Clinical characteristics of dogs presenting with vomiting as a gastrointestinal sign of chronic enteropathy.

Vomiting is a major gastrointestinal (GI) sign of chronic enteropathy (CE) in dogs. Previous studies have reported clinical characteristics of dogs with CE, who developed diarrhea with or without vomiting as GI signs. However, to characterize clinical features of dogs with CE appropriately, dogs presenting with vomiting without diarrhea should be included in the analysis. Thus, this study aimed to characterize clinical features and outcomes of dogs that presented with vomiting without diarrhea. Based on their presenting GI signs, we retrospectively classified 66 dogs with CE into "Vomiting", "Diarrhea", or "Vomiting and diarrhea" groups and compared clinical and histological characteristics of each group. We found that 18 of the 66 dogs with CE (27%) presented with vomiting without diarrhea as a GI sign. Compared to the other 2 groups, the Vomiting group was significantly associated with food-responsive enteropathy (FRE), Beagle, lower clinical severity scores, higher plasma albumin levels, and higher histological scores for eosinophils in the duodenal lamina propria according to the univariate analysis. The multivariate analysis revealed that FRE and higher histological scores for eosinophils in the duodenal lamina propria were significant variables in the Vomiting group. Moreover, the survival time was the longest in the Vomiting group among dogs with CE. These findings are of clinical significance as they indicate that presenting with vomiting without diarrhea may not only be helpful in differentiating FRE from the other types of CE, but also in predicting the prognosis.

House dust mite-derived serine protease upregulates gene expression of interleukin-33 in canine keratinocytes via protease-activated receptor-2.

BACKGROUND: The involvement of interleukin (IL)-33 produced by keratinocytes has been suggested in the pathogenesis of canine atopic dermatitis (cAD). House dust mite (HDM)-derived proteases induce the production of various cytokines and chemokines in keratinocytes via protease-activated receptor-2 (PAR-2); however, their effects on IL-33 mRNA expression in canine keratinocytes have not been determined. HYPOTHESIS/OBJECTIVE: To clarify whether HDM-derived proteases induce IL-33 mRNA expression in canine keratinocytes via PAR-2. METHODS AND MATERIALS: Expression of IL-33 mRNA was quantified by real-time PCR in a cell line of canine progenitor epidermal keratinocytes (CPEK) stimulated with Dermatophagoides farinae (Der f) whole body extract, Der f pre-treated with cysteine protease and serine protease inhibitors, and trypsin. Trypsin and Der f-mediated IL-33 mRNA expression also was measured in CPEK cells treated with a PAR-2 antagonist. RESULTS: Der f enhanced IL-33 mRNA expression in CPEK cells in incubation time- and dose-dependent manners. Der f pre-treated with a serine protease inhibitor, and not a cysteine protease inhibitor, abrogated an increase in IL-33 mRNA expression in CPEK cells. Trypsin also enhanced IL-33 mRNA expression in CPEK cells. Trypsin-mediated IL-33 mRNA expression was completely abolished by a PAR-2 antagonist, while Der f-mediated IL-33 mRNA expression was partially and significantly diminished by it. CONCLUSIONS AND CLINICAL RELEVANCE: Der f-derived serine protease upregulated IL-33 mRNA expression in CPEK cells at least in part via PAR-2. These findings suggest that HDM may be involved in the development of C AD by increasing IL-33 mRNA expression in keratinocytes.

The Effect of Piceatannol from Passion Fruit (Passiflora edulis) Seeds on Metabolic Health in Humans.

Animal studies have shown the beneficial effects of piceatannol on metabolic health; however, there is a lack of human studies designed to examine these effects. The objective of this study was to investigate the effects of piceatannol on metabolic health in humans. This randomized, placebo-controlled study was conducted on 39 subjects, including 10 overweight men and 9 overweight women (BMI ≥ 25), as well as 10 non-overweight men and 10 non-overweight women (BMI < 25). Subjects received piceatannol (20 mg/day) or placebo capsules for eight weeks in a random order. The primary outcome was the effect of piceatannol on glucose-metabolism, including insulin sensitivity. The secondary outcomes were the effects on other parameters, including blood pressure (BP), heart rate (HR), endothelial function, lipids, inflammation, oxidative stress, mood status, and Sirt1 and phospho-AMP-activated kinase (p-AMPK) expression in isolated peripheral blood mononuclear cells (PBMNCs). Supplementation with piceatannol in overweight men reduced serum insulin levels, HOMA-IR, BP and HR. Other groups, including non-overweight men, as well as overweight and non-overweight women, showed no beneficial effects on insulin sensitivity, BP and HR. Furthermore, piceatannol is not associated with other data, including body weight (BW), body composition, endothelial function, lipids, inflammation, oxidative stress, mood status, and Sirt1/p-AMPK expression in PBMNCs. In conclusion, supplementation with piceatannol can improve metabolic health, including insulin sensitivity, BP and HR, in overweight men.