Sterol regulatory element-binding protein-1 (SREBP-1) plays a central role in transcriptional regulation of genes for hepatic lipid synthesis that utilizes diet-derived nutrients such as carbohydrates and amino acids, and expression of SREBP-1 exhibits daily rhythms with a peak in the nocturnal feeding period under standard housing conditions of mice. Here, we report that the Srebp-1 expression rhythm shows time cue-independent and Clock mutation-sensitive circadian nature, and is synchronized with varied photoperiods apparently through entrainment of locomotor activity and food intake. Fasting caused diminution of Srebp-1 expression, while diabetic db/db and ob/ob mice showed constantly high expression with loss of rhythmicity. Time-restricted feedings during mid-light and mid-dark periods exhibited differential effects, the latter causing more severe damping of the oscillation. Therefore, "when to eat in a day (the light/dark cycle)," rather than "whenever to eat in a day," is a critical determinant to shape the daily rhythm of Srebp-1 expression. We further found that a high-carbohydrate diet and a high-protein diet, as well as a high-fat diet, cause phase shifts of the oscillation peak into the light period, underlining the importance of "what to eat." Daily rhythms of SREBP-1 protein levels and Akt phosphorylation levels also exhibited nutrientresponsive changes. Taken together, these findings provide a model for mechanisms by which time of day and nutrients in feeding shape daily rhythms of the Srebp-1 expression and possibly a number of other physiological functions with interindividual and interdaily differences in human beings and wild animals subjected to day-by-day changes in dietary timing and nutrients.The circadian timekeeping system for physiology and behavior in mammals consists of a whole-body network of cell-intrinsic oscillators that rely on activation/repression-alternating feedback loops of clock gene expression (1, 2). Daily expression rhythms of clock genes as oscillation generators are synchronized (entrained) to the light/dark cycle in the central pacemaker localized to the suprachiasmatic nucleus (SCN) 3 of the hypothalamus, whereas they are predominantly entrained to the feeding/fasting cycle in other brain regions and peripheral organs (3-5). On the other hand, it is poorly understood how daily rhythms of a large number of physiological functions as oscillation outputs are shaped and coordinated with each other.As a typical example of daily rhythms of liver functions exhibiting a wide spectrum of variety, we (6, 7) previously studied regulatory mechanisms for daily expression rhythms of the gene encoding Spot14 (8, 9) a regulatory protein stimulating lipid biosynthesis that is one of the most closely feeding-related functions in the liver. Because the Spot14 promoter is under the control (10) of sterol regulatory element-binding protein (SREBP)-1c (11, 12) a pivotal transcriptional regulator of genes for triglyceride synthesis, we here focused on Srebp-1 expression rhythms in the mous...
-Background:It is well known that Langerhans cells (LCs) work as the primary orchestrators in the polarization of the immune milieu towards a T helper type 1 (Th1) or a Th2 immune response. In this study, we investigated the effects of macrolide antibiotics on Th1 cell and Th2 cell development mediated by LCs. Methods: LC-like dendritic cells (LDCs) were generated from mouse bone marrow cells and used as substitutes for LCs. Mice were primed with ovalbumin (OVA) peptide-pulsed LDCs, which had been treated with each macrolide antibiotic, via the hind footpad. After 5 days, the cytokine response in the popliteal lymph nodes was investigated by enzyme-linked immunosorbent assay. The expression of cell surface molecules on LDCs was investigated using reverse transcriptase polymerase chain reaction. Results: Injection of OVA peptide-pulsed LDCs, which had been treated with josamycin or spiramycin, inhibited Th2 cell development as represented by down-regulation of interleukin (IL)-4 production as well as Th1 cell development as represented by downregulation of interferon (IFN)- production. This inhibition of Th1 cell and Th2 cell development was associated with suppression of CD86 and T-cell immunoglobulin and mucin domain-containing protein (TIM)-4 expression, respectively, in LDCs. Furthermore, Staphylococcus aureus strains isolated from skin lesions of patients with atopic dermatitis (AD) were more susceptible to josamycin than to spiramycin. Conclusions: These results suggest that topical application of josamycin to AD lesions colonized with S. aureus would be beneficial for control of AD by acting on both superficial S. aureus and epidermal LCs, and inhibiting the development of Th2 cells.
It is well known that Langerhans cells (LCs) work as the primary orchestrators in the polarization of the immune milieu towards a T helper type 1 (Th1) or T helper type 2 (Th2) response. In this study, we investigated the effects of tacrolimus and betamethasone, each used as topical applications in atopic dermatitis (AD), on Th2 cell development mediated by LCs. LC-like dendritic cells (LDCs) were generated from mouse bone marrow cells and used as substitutes for LCs. Mice were primed with ovalbumin (OVA) peptide-pulsed LDCs, which had been treated with tacrolimus or betamethasone, via the hind footpad. After 5 d, the cytokine response in the popliteal lymph nodes was investigated by enzyme-linked immunosorbent assay. The expression of cell surface molecules on LDCs was investigated via reverse transcriptase polymerase chain reaction. Administration of OVA peptide-pulsed LDCs, which had been treated with betamethasone, inhibited Th2 cell development, as represented by the down-regulation of interleukin-4 production, and also inhibited Th1 cell development, represented by the down-regulation of interferon-γ production. However, tacrolimustreated LDCs did not induce such inhibition of the development of Th1 and Th2 cells. The inhibition of Th1 and Th2 cell development was associated with the suppression of CD40 and T-cell immunoglobulin, and mucin domain-containing protein (TIM)-4 expression, respectively, in LDCs. These results suggest that the topical application of betamethasone to skin lesions of patients with AD acts on epidermal LCs, and may inhibit the development of Th2 cells, thus being of benefit for the control of AD.
Table of ContentsA1 Pirfenidone inhibits TGF-b1-induced extracellular matrix production in nasal polyp-derived fibroblastsJae-Min Shin, Heung-Man Lee, Il-Ho ParkA2 The efficacy of a 2-week course of oral steroid in the treatment of chronic spontaneous urticaria refractory to antihistaminesHyun-Sun Yoon, Gyeong Yul ParkA3 The altered distribution of follicular t helper cells may predict a more pronounced clinical course of primary sjögren’s syndromeMargit ZeherA4 Betamethasone suppresses Th2 cell development induced by langerhans cell like dendritic cellsKatsuhiko Matsui, Saki Tamai, Reiko IkedaA5 An evaluation of variousallergens in cases of allergic bronchial asthma at lucknow and neighbouring districts by intradermal skintestDrsushil Suri, Dranu SuriA6 Evaluation ferqency of ADHD in childhood asthmaMarzieh Heidarzadeh AraniA7 Steven johnson syndrome caused by typhoid fever in a childAzwin Lubis, Anang EndaryantoA8 Chronic Bronchitis with Radio Contrast Media Hypersensitivity: A Case with Hypothesized GINA Step 1 AsthmaShinichiro KogaA9 The association between asthma and depression in Korean adult : An analysis of the fifth korea national health and nutrition examination survey (2010-2012)Lee Ju SukA10 Management of allergic disease exacerbations in pregnancyYasunobu TsuzukiA11 Subcutaneous immunotherapy mouse model for atopic dermatitisSeo Hyeong Kim, Jung U Shin, Ji Yeon Noh, Shan Jin, Shan Jin, Hemin Lee, Jungsoo Lee, Chang Ook Park, Kwang Hoon Lee, Kwang Hoon LeeA12 Atopic disease and/or atopy are risk factors for local anesthetic allergy in patients with history of hypersensitivity reactions to drugs?Fatma Merve TepetamA13 Food hypersensitivity in patients with atopic dermatitis in KoreaChun Wook Park, Jee Hee Son, Soo Ick Cho, Yong Se Cho, Yun Sun Byun, Yoon Seok Yang, Bo Young Chung, Hye One Kim, Hee Jin ChoA14 Anaphylaxis caused by an ant (Brachyponera chinensis) in JapanYoshinori Katada, Toshio Tanaka, Akihiko Nakabayashi, Koji Nishida, Kenichi Aoyagi, Yuki Tsukamoto, Kazushi Konma, Motoo Matsuura, Jung-Won Park, Yoshinori Harada, Kyoung Yong Jeong, Akiko Yura, Maiko YoshimuraA15 Anti-allergic effect of anti-IL-33 by suppression of immunoglobulin light chain and inducible nitric oxide synthaseTae-Suk Kyung, Young Hyo Kim, Chang-Shin Park, Tae Young Jang, Min-Jeong Heo, Ah-Yeoun Jung, Seung-Chan YangA16 Food hypersensitivity in patients with chronic urticaria in KoreaHye One Kim, Yong Se Cho, Yun Sun Byun, Yoon Seok Yang, Bo Young Chung, Jee Hee Son, Chun Wook Park, Hee Jin ChoA17 Dose optimizing study of a depigmented polymerized allergen extract of phleum pollen by means of conjunctival provocation test (CPT)Angelika Sager, Oliver PfaarA18 Correlation of cutaneous sensitivity and cytokine response in children with asthmaAmit Agarwal, Meenu Singh, Bishnupda Chatterjee, Anil ChauhanA19 Colabomycin E, a Streptomycete-Derived Secondary Metabolite, Inhibits Proinflammatory Cytokines in Human Monocytes/MacrophagesIlja Striz, Eva Cecrdlova, Katerina Petrickova, Libor Kolesar, Alena Sekerkova, Veronika Svachov...
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