Inhibitory Effects of Fermented Brown Rice on Induction of Acute Colitis by Dextran Sulfate Sodium in Rats

Although the pathogenic mechanisms of inflammatory bowel diseases are not fully understood, colonic microbiota may affect the induction of colonic inflammation, and some probiotics and prebiotics have been reported to suppress colitis. The inhibitory effects of brown rice fermented by Aspergillus oryzae (FBRA), a fiber-rich food, on the induction of acute colitis by dextran sulfate sodium (DSS) were examined. Feeding a 5% and 10% FBRA-containing diet significantly decreased the ulcer and erosion area in the rat colon stained with Alcian blue. In another experiment, 10% FBRA feeding decreased the ulcer index (percentage of the total length of ulcers in the full length of the colon) and colitis score, which were determined by macroscopic observation. It also decreased myeloperoxidase activity in the colonic mucosa. Viable cell numbers of Lactobacillus in the feces decreased after DSS administration and was reversely correlated with severity of colitis, while the cell number of Enterobacteriaceae increased after DSS treatment and was positively correlated with colitis severity. These results indicate that FBRA has a suppressive effect on the induction of colitis by DSS and suggest FBRA-mediated modification of colonic microbiota.     

Establishment of a leukaemic cell line from a patient with acquisition of chromosomal abnormalities during disease progression in myelodysplastic syndrome

Summary. A cell line designated SKM-1 was newly established from leukaemic cells of a 76-year-old Japanese male patient with monoblastic leukaemia following myelodysplastic syndrome (MDS). The cells were obtained from peripheral blood of the patient when he lost multiple point mutations of ras genes with acquisition of chromosomal abnormalities during disease progression in MDS. The cells grew as a single floating cell, and have been continuously growing with the morphological characteristics of immature monoblasts by serial passages during the past 42 months with a doubling time of about 48 h. By cytochemical analysis. the cloned cells were positive for butyrate esterase, but negative for the Epstein-Barr virus associated nuclear antigen. Phenotypic analysis revealed the expression of myelomonocyte specific antigens such as CD4, CD13, CD33 and HLA-DR. Cells from the primary peripheral blood and those from SO passages of the SKM-1 cell line both possessed no activated ras genes but showed karyotype abnormalities with 46.XY, del(9)(q13;q22), der(17) t(17:?)(p13:?). The SKM-1 cells have two mutations in p53 gene and overexpress the pS3 products. This cell line may contribute to a better understanding of molecular mechanisms in the progression from MDS to myelogenous leukaemia.     

An effective strategy to reduce blood pressure after forest walking in middle-aged and aged people

[Purpose] Forest walking may be effective for human health, but little information is available about effects of energy expenditure on blood pressure responses after forest walking. The aim of this study was to investigate the relationship between the activity energy expenditure and changes in blood pressure in individuals after forest walking. [Subjects] The subjects were 54 middle-aged and elderly people. [Methods] All subjects walked in the forest for approximately 90 min. Blood pressure, salivary amylase, and the Profile of Mood States were evaluated before and after forest walking, and activity energy expenditure was monitored throughout forest walking. Subjects were divided into two groups according to mean arterial pressure changes: a responder group (>5% decreases) and a nonresponder group (<5%). [Results] Forest walking significantly reduced the mean arterial pressure and improved the Profile of Mood States in both groups. Activity energy expenditure was related to changes in mean arterial pressure in the responder group, while this relation was not observed in the nonresponder group. Differential activity energy expenditure did not strongly affect improvement of the Profile of Mood States. [Conclusion] Greater walking-related greater activity energy expenditure might be required to accentuate physiological beneficial effects on in middle-aged and aged people. Furthermore, the forest environment per se can attenuate psychological stress.Key words: Hypertension, Profile of Mood States, Responder and nonresponder     

Resolvin E1 inhibits dendritic cell migration in the skin and attenuates contact hypersensitivity responses

Resolvin E1 (RvE1) is a lipid mediator derived from ω3 polyunsaturated fatty acids that exerts potent antiinflammatory roles in several murine models. The antiinflammatory mechanism of RvE1 in acquired immune responses has been attributed to attenuation of cytokine production by dendritic cells (DCs). In this study, we newly investigated the effect of RvE1 on DC motility using two-photon microscopy in a contact hypersensitivity (CHS) model and found that RvE1 impaired DC motility in the skin. In addition, RvE1 attenuated T cell priming in the draining lymph nodes and effector T cell activation in the skin, which led to the reduced skin inflammation in CHS. In contrast, leukotriene B4 (LTB4) induced actin filament reorganization in DCs and increased DC motility by activating Cdc42 and Rac1 via BLT1, which was abrogated by RvE1. Collectively, our results suggest that RvE1 attenuates cutaneous acquired immune responses by inhibiting cutaneous DC motility, possibly through LTB4-BLT1 signaling blockade.Following the well-known epidemiological study conducted in Northwest Greenland in the 1970s (Dyerberg et al., 1978), several clinical assessments have indicated that a diet rich in ω3 polyunsaturated fatty acids (PUFAs) has beneficial effects in various inflammatory diseases, including asthma, psoriasis, inflammatory bowel diseases, and rheumatoid arthritis (Horrobin, 1987). Although it remains unclear how ω3 PUFAs exert such antiinflammatory effects, recent studies have identified several derivatives of ω3 PUFAs that possess strong antiinflammatory effects (Serhan et al., 2008; Tull et al., 2009). Resolvin E1 (RvE1) is one such antiinflammatory lipid mediator.RvE1 is known to exert its actions through two receptors, BLT1 and ChemR23 (Arita et al., 2007). RvE1 binds to BLT1, a G protein–coupled receptor for leukotriene B4 (LTB4), and inhibits BLT1 signals (Arita et al., 2007). In addition, RvE1 exhibits an agonistic activity toward ChemR23 (Arita et al., 2007), a G protein–coupled receptor for chemerin. The antiinflammatory effects of RvE1 have been demonstrated in acute innate immune inflammation, such as peritonitis (Arita et al., 2007) and colitis (Arita et al., 2005b). In these models, RvE1 exerted its antiinflammatory effects by inhibiting neutrophil infiltration into the inflammatory foci through a blockade of LTB4-BLT1 signaling in neutrophils (Haas-Stapleton et al., 2007). In contrast, few studies have been conducted on the effect of RvE1 on acquired immune responses, in which DCs and T cells play major roles in the development. In these studies, the attenuated cytokine production, such as IL-12 and IL-23, from DCs is considered as the major mechanism by which RvE1 exerts the antiinflammatory effects (Arita et al., 2005a; Haworth et al., 2008). However, the effect of RvE1 on DC motility has not been investigated in the context of acquired immunity.In the peripheral tissues such as the skin, DCs migrate in an amoeboid movement that requires actin polymerization via activation of the Rho family of small GTPases, such as Cdc42, Rac, and Rho A (Lämmermann and Germain, 2014). In acquired immunity such as contact hypersensitivity (CHS), upon uptake of foreign antigens, DCs migrate to the draining LNs (dLNs) via lymphatic vessels to establish sensitization by inducing the antigen-specific T cell differentiation (Honda et al., 2013). In elicitation, DC migration to form DC–T cell clustering is required for efficient antigen presentation in situ (Natsuaki et al., 2014). Thus, active DC motility is an essential factor for acquired immunity.In this study, we investigated the effects and underlying mechanisms of RvE1 on DC motility using a CHS model, which is a prototype of delayed-type hypersensitivity in the skin mediated by IFN-γ (Mori et al., 2008; Honda et al., 2013). RvE1 inhibited cutaneous DC migration into the dLNs and suppressed antigen-specific T cell induction in the sensitization phase. In addition, live imaging analysis revealed that RvE1 inhibited cutaneous DC motility and cluster formation in the skin, which subsequently attenuated activation of effector T cells in the skin in the elicitation phase of CHS. Intriguingly, LTB4 induced actin filament reorganization in DCs and increased DC motility by activating Cdc42 and Rac1 via BLT1, which was abrogated by RvE1. These results suggest that RvE1 exerts its antiinflammatory effects in cutaneous acquired immunity by inhibiting DC motility, possibly through an LTB4-BLT1 signaling blockade.