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TGF-beta AND vitamin D3

Zhu-Xia Tan, Yuan-Hua Chen, Shen Xu, Hou-Ying Qin, Cheng Zhang, Hui Zhao, De-Xiang Xu
Early pulmonary inflammation and epithelial-mesenchymal transition (EMT) play important roles during lung fibrosis. Increasing evidence demonstrates that calcitriol, the active form of vitamin D3, has anti-inflammatory activities. The aim of this study was to investigate the effects of calcitriol on bleomycin (BLM)-induced early pulmonary inflammation and subsequent EMT. Mice were intratracheally injected with BLM (3.0mg/kg). In three calcitriol+BLM groups, mice were intraperitoneal (i.p.) injected with different doses of calcitriol (0...
January 5, 2016: Toxicology Letters
Julia Åivo, Arno Hänninen, Jorma Ilonen, Merja Soilu-Hänninen
BACKGROUND: Deficiency of vitamin D is an environmental risk factor for MS. Vitamin D has immunomodulatory effects, including promotion of T-cell differentiation into T-regulatory cells, which produces regulatory cytokines including TGF-β. Increasing serum vitamin D levels have been associated with decreased disease activity in MS patients, but there are only few studies concerning the immunological effects of vitamin D supplementation in MS. In this study we investigated the effect of weekly supplementation of vitamin D3 or placebo on serum levels of multiple cytokines in patients with relapsing remitting MS...
March 15, 2015: Journal of Neuroimmunology
A Vijayendra Chary, R Hemalatha, M Seshacharyulu, M Vasudeva Murali, D Jayaprakash, B Dinesh Kumar
Regulatory T cells and IgE receptors (CD23 and CD21) on B cells were assessed in vitamin D deficient pregnant women. For this, 153 pregnant women were recruited from a government hospital and were categorized into three groups based on 25-hydroxyvitamin D3 (25(OH)D3) status. Regulatory T cell population (Treg cells) and CD23/CD21 expression on B cells were quantified by FACS ARIA II in maternal blood at third trimester; and the same parameters were evaluated in cord blood soon after delivery. In addition, TGF β and IL-10 were quantified in maternal and cord blood by using Milliplex kits...
April 2015: Journal of Steroid Biochemistry and Molecular Biology
Nikhil N Kulkarni, Zhiqian Yi, Carolin Huehnken, Birgitta Agerberth, Gudmundur H Gudmundsson
Antimicrobial peptides (AMPs) constitute an indispensable arm of innate immunity against infectious microbes in humans. Induction of endogenous AMPs may become an alternative therapy against infections. Our previous studies have demonstrated phenylbutyrate (PBA) as a novel inducer of the AMPs cathelicidin (encoded by the CAMP gene) and human beta-defensin-1 in the human bronchial epithelial cell line VA10. In this work, we have continued by studying molecular mechanisms of PBA mediated induction of LL-37 expression and associated pathways in the human bronchial epithelial cell line VA10...
February 2015: Molecular Immunology
A Vijayendra Chary, R Hemalatha, M Seshacharyulu, M Vasudeva Murali, D Jayaprakash, B Dinesh Kumar
Regulatory T cells and IgE receptors (CD23 and CD21) on B cells were assessed in vitamin D deficient pregnant women. For this, 153 pregnant women were recruited from a government hospital and were categorized into three groups based on 25-hydroxyvitamin D3 (25(OH)D3) status. Regulatory T cell population (Treg cells) and CD23/CD21 expression on B cells were quantified by FACS ARIA II in maternal blood at third trimester; and the same parameters were evaluated in cord blood soon after delivery. In addition, TGF β and IL-10 were quantified in maternal and cord blood by using Milliplex kits...
March 2015: Journal of Steroid Biochemistry and Molecular Biology
Fahimeh Lavi Arab, Maryam Rastin, Fatemeh Faraji, Shahrzad Zamani Taghizadeh Rabe, Nafise Tabasi, Mahdieh Khazaee, Dariush Haghmorad, Mahmoud Mahmoudi
CONTEXT: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease which is characterized by the presence of auto-reactive T cell and anti-ds DNA antibodies. Treg cells are crucial for maintaining immunologic self-tolerance and are shown to be reduced in SLE patients. 1,25-Dihydroxyvitamin D3 has immunomedulatory effects on the immune system and has recently received substantial attention. OBJECTIVE: In this study we evaluated the effects of 1,25-dihydroxyvitamin D3 on Treg cells and related cytokines in lupus-like induced mice model...
February 2015: Immunopharmacology and Immunotoxicology
Joshua D Solomon, Marjet D Heitzer, Teresa T Liu, Jan H Beumer, Robert A Parise, Daniel P Normolle, Damien A Leach, Grant Buchanan, Donald B DeFranco
UNLABELLED: Patients with prostate cancer treated with androgen deprivation therapy (ADT) eventually develop castrate-resistant prostate cancer (CRPC). 1,25-Dihydroxyvitamin D3 (1,25D3/calcitriol) is a potential adjuvant therapy that confers antiproliferative and pro-differentiation effects in vitro, but has had mixed results in clinical trials. The impact of the tumor microenvironment on 1,25D3 therapy in patients with CRPC has not been assessed. Transforming growth factor β (TGFβ), which is associated with the development of tumorigenic "reactive stroma" in prostate cancer, induced vitamin D3 receptor (VDR) expression in the human WPMY-1 prostate stromal cell line...
August 2014: Molecular Cancer Research: MCR
Emma S Chambers, Duangchan Suwannasaen, Elizabeth H Mann, Zoe Urry, David F Richards, Ganjana Lertmemongkolchai, Catherine M Hawrylowicz
A high prevalence of vitamin D insufficiency and deficiency exists worldwide, which is associated with an increased incidence and severity of a range of immune-mediated diseases. This has resulted in considerable interest in the immunodulatory functions of vitamin D. The active form of vitamin D, 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3], has been shown to increase the frequency of Foxp3(+) CD4(+) T regulatory (Treg) cells when present at high concentrations or under strong T-cell stimulation in culture. Supporting evidence exists in vivo for a positive association between serum 25(OH)D and Foxp3(+) Treg cell numbers in humans...
September 2014: Immunology
Pawel Zerr, Stefan Vollath, Katrin Palumbo-Zerr, Michal Tomcik, Jingang Huang, Alfiya Distler, Christian Beyer, Clara Dees, Kolja Gela, Oliver Distler, Georg Schett, Jörg H W Distler
BACKGROUND: Vitamin D receptor (VDR) is a member of the nuclear receptor superfamily. Its ligand, 1,25-(OH)2D, is a metabolically active hormone derived from vitamin D3. The levels of vitamin D3 are decreased in patients with systemic sclerosis (SSc). Here, we aimed to analyse the role of VDR signalling in fibrosis. METHODS: VDR expression was analysed in SSc skin, experimental fibrosis and human fibroblasts. VDR signalling was modulated by siRNA and with the selective agonist paricalcitol...
March 2015: Annals of the Rheumatic Diseases
Thea K Wöbke, Andreas von Knethen, Dieter Steinhilber, Bernd L Sorg
CD69 is a transmembrane lectin that can be expressed on most hematopoietic cells. In monocytes, it has been functionally linked to the 5-lipoxygenase pathway in which the leukotrienes, a class of highly potent inflammatory mediators, are produced. However, regarding CD69 gene expression and its regulatory mechanisms in monocytes, only scarce data are available. Here, we report that CD69 mRNA expression, analogous to that of 5-lipoxygenase, is induced by the physiologic stimuli transforming growth factor-β (TGF-β) and 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3) in monocytic cells...
2013: PloS One
Stefan Tukaj, Piotr Trzonkowski, Cecylia Tukaj
Inflammatory response has been recognized as a central feature in the development and progression of atherosclerosis, and VSMCs (Vascular Smooth Muscle Cells) - the main cellular component of media, play an important role in this process. Many reports indicate that the biologically active vitamin D metabolite - 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3) = calcitriol), besides its well established role in calcium homeostasis, plays an essential role in the regulation of the inflammation process. The aim of this study was to determine the regulatory effects of calcitriol, applied at two supra-physiological doses (10 nM and 100 nM), in VSMC culture...
2012: Acta Biochimica Polonica
Michael Lohmann, Gudrun Walenda, Hatim Hemeda, Sylvia Joussen, Wolf Drescher, Stefan Jockenhoevel, Gabriele Hutschenreuter, Martin Zenke, Wolfgang Wagner
The regenerative potential declines upon aging. This might be due to cell-intrinsic changes in stem and progenitor cells or to influences by the microenvironment. Mesenchymal stem cells (MSC) raise high hopes in regenerative medicine. They are usually culture expanded in media with fetal calf serum (FCS) or other serum supplements such as human platelet lysate (HPL). In this study, we have analyzed the impact of HPL-donor age on culture expansion. 31 single donor derived HPLs (25 to 57 years old) were simultaneously compared for culture of MSC...
2012: PloS One
Masayoshi Yamaguchi, M Neale Weitzmann
Vitamin D is essential for optimal calcium absorption needed for maintaining normal bone mineral density (BMD). Consequently, vitamin D-deficiency leads to poorly mineralized bone with diminished strength and load bearing capacity. Surprisingly, several animal and clinical studies have identified suppressive effects of high dose vitamin D supplementation on bone formation. These data suggest that while vitamin D is necessary for basal bone homeostasis, excessive concentrations may be detrimental to the skeleton...
May 2012: International Journal of Molecular Medicine
Serhat Isik, Ufuk Ozuguz, Yasemin Ates Tutuncu, Gonul Erden, Dilek Berker, Kadir Acar, Yusuf Aydin, Gulhan Akbaba, Nafiye Helvaci, Serdar Guler
BACKGROUND: Transforming growth factor-beta 1 (TGF-β1) contributes to tissue repair by promoting tissue fibrosis, and elevations have been reported in patients with bone marrow fibrosis. The aim of this study was to evaluate the relationship between TGF-β1 levels and vitamin D deficiency. METHODS: All patients presenting to the outpatient Endocrinology and Metabolic Diseases clinic between June and September of 2008 were approached, and consenting patients who were deemed suitable candidates were enrolled...
January 2012: European Journal of Internal Medicine
Angelic M G van der Aar, Darya S Sibiryak, Ghaith Bakdash, Toni M M van Capel, Hanneke P M van der Kleij, Dirk-Jan E Opstelten, Marcel B M Teunissen, Martien L Kapsenberg, Esther C de Jong
BACKGROUND: The vitamin D metabolite 1,25(OH)2D3 (VitD3) is a potent immunosuppressive drug and, among others, is used for topical treatment of psoriasis. A proposed mechanism of VitD3-mediated suppression is priming of dendritic cells (DCs) to induce regulatory T (Treg) cells. OBJECTIVE: Currently, there is confusion about the phenotype of VitD3-induced Treg cells and the DC-derived molecules driving their development. We investigated Treg cell induction after VitD3 priming of 2 distinct skin DC subsets: Langerhans cells (LCs) and dermal dendritic cells (DDCs)...
June 2011: Journal of Allergy and Clinical Immunology
James L Kreindler, Chad Steele, Nikki Nguyen, Yvonne R Chan, Joseph M Pilewski, John F Alcorn, Yatin M Vyas, Shean J Aujla, Peter Finelli, Megan Blanchard, Steven F Zeigler, Alison Logar, Elizabeth Hartigan, Marcia Kurs-Lasky, Howard Rockette, Anuradha Ray, Jay K Kolls
Allergic bronchopulmonary aspergillosis (ABPA) is caused by a dominant Th2 immune response to antigens derived from the opportunistic mold Aspergillus, most commonly Aspergillus fumigatus. It occurs in 4%-15% of patients with cystic fibrosis (CF); however, not all patients with CF infected with A. fumigatus develop ABPA. Therefore, we compared cohorts of A. fumigatus-colonized CF patients with and without ABPA to identify factors mediating tolerance versus sensitization. We found that the costimulatory molecule OX40 ligand (OX40L) was critical in driving Th2 responses to A...
September 2010: Journal of Clinical Investigation
Kayhan T Nouri-Aria
Allergic diseases such as asthma, rhinitis and eczema are increasing in prevalence worldwide, in particular in industrialised countries affecting up to 20% of the population. Regulatory T-cells (Tregs) have been shown to be critical in T-cell homeostasis and in the maintenance of immune responses, such as prevention of autoimmunity and hampering allergic diseases. The so-called 'natural' CD4+CD25+ Tregs and/or IL-10-producing Tr1 cells have been shown to be responsible for the protection of immune tolerance and intact immune reactions following exposure to allergens such as aeroallergens or food allergens...
2009: Advances in Experimental Medicine and Biology
Mohammad Tezval, Hossein Tezval, Klaus Dresing, Ewa Klara Stuermer, Martina Blaschke, Klaus Michael Stuermer, Heide Siggelkow
Urocortin-1 (UCN) a corticotropin releasing-factor (CRF) related peptide, has been found to be expressed in many different tissues like the central nervous system, the cardiovascular system, adipose tissue, and skeletal muscle. The effects of UCN are mediated via stimulation of CRF-receptors 1 and 2 (CRFR1 and 2, CRFR's) with a high affinity for CRFR2. It has been shown that the CRF-related peptides and CRFR's are involved in the regulation of stress-related endocrine, autonomic and behavioural responses. Using immunocytochemistry, immunohistochemistry and RT-PCR, we now can show the differentiation dependent expression of UCN mRNA and peptide in human mesenchymal progenitor cells (MSCs) directed to the osteoblastic phenotype for the first time...
October 2009: Journal of Molecular Histology
Zhuo-Min Jiao, Yu-Hong Fu, Jin Fu, Feng Zhang, Wei-Zhi Wang
OBJECTIVE: To investigate the mechanism of rapid amelioration of the pathological changes in experimental allergic encephalomyelitis (EAE) by 1, 25-dihydroxyvitamin D(3) [1, 25-(OH)(2)D(3)]. METHODS: Forty Lewis rats were immunized with myelin basic protein in complete Freud's adjuvant so as to establish ESE animal models and then randomly divided into 4 equal groups: prevention group, fed with 1, 25-(OH)(2)D(3) since day 0 for 10 days, prevention-control group fed with peanut oil for 10 days, treatment group fed with 1, 25-(OH)(2)D(3) since the appearance of EAE symptoms (generally since day 10 or 11), and treatment-control group fed with peanut oil since the appearance of EAE symptoms...
August 26, 2008: Zhonghua Yi Xue za Zhi [Chinese medical journal]
Kayhan T Nouri-Aria, Stephen R Durham
Allergic diseases such as asthma, rhinitis, and eczema are increasing in prevalence and affect about 15% of the population in countries such as the UK or USA. Regulatory T cells (T(Regs)) have been shown to be critical in the maintenance of immune responses and T cell homeostasis. For example, depletion of CD4(+)CD25(+) T(Regs) from mice resulted in the development of multiorgan autoimmune diseases. So-called 'natural' CD4(+)CD25(+) T(Regs) and/or IL-10-producing Tr-1 cells are capable of suppressing Th2 responses to allergens in health, whereas such inhibition is attenuated in allergic conditions...
December 2008: Inflammation & Allergy Drug Targets
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