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Ppar tuberculosis

Shyamashree Dasgupta, Ramesh Chandra Rai
The success of Mycobacterium tuberculosis (Mtb) as a pathogen stems from its ability to manipulate the host macrophage towards increased lipid biogenesis and lipolysis inhibition. Inhibition of lipolysis requires augmented uptake of glucose into the host cell causing an upregulation of the glucose transporters GLUT1 and GLUT3 on the cell surface. Mechanism behind this upregulation of the GLUT proteins during Mtb infection is hitherto unknown and demands intensive investigation in order to understand the pathways linked with governing them...
March 2018: Molecular and Cellular Biochemistry
Yi Sak Kim, Hye-Mi Lee, Jin Kyung Kim, Chul-Su Yang, Tae Sung Kim, Mingyu Jung, Hyo Sun Jin, Sup Kim, Jichan Jang, Goo Taeg Oh, Jin-Man Kim, Eun-Kyeong Jo
The role of peroxisome proliferator-activated receptor α (PPAR-α) in innate host defense is largely unknown. In this study, we show that PPAR-α is essential for antimycobacterial responses via activation of transcription factor EB (TFEB) transcription and inhibition of lipid body formation. PPAR-α deficiency resulted in an increased bacterial load and exaggerated inflammatory responses during mycobacterial infection. PPAR-α agonists promoted autophagy, lysosomal biogenesis, phagosomal maturation, and antimicrobial defense against Mycobacterium tuberculosis or M...
April 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
Qin Pan, Jiamin Yan, Qi Liu, Chunhui Yuan, Xiao-Lian Zhang
Mannose-capped lipoarabinomannan (ManLAM) is an immunomodulatory epitope of Mycobacterium tuberculosis (Mtb). An aptamer (ZXL1) that specifically binds to ManLAM from the virulent Mtb H37Rv strain was previously generated and it was found that ZXL1 functions as an antagonist, inhibiting the ManLAM-induced immunosuppression of DCs. In the present study, it was found that ZXL1 inhibits Mtb entry into murine macrophages and that ZXL1 enhances IL-1β and IL-12 mRNA expression and cytokine production in ManLAM-treated macrophages but decreases IL-10 production...
February 2017: Microbiology and Immunology
Rustin R Lovewell, Christopher M Sassetti, Brian C VanderVen
The interplay between Mycobacterium tuberculosis lipid metabolism, the immune response and lipid homeostasis in the host creates a complex and dynamic pathogen-host interaction. Advances in imaging and metabolic analysis techniques indicate that M. tuberculosis preferentially associates with foamy cells and employs multiple physiological systems to utilize exogenously derived fatty-acids and cholesterol. Moreover, novel insights into specific host pathways that control lipid accumulation during infection, such as the PPARγ and LXR transcriptional regulators, have begun to reveal mechanisms by which host immunity alters the bacterial micro-environment...
February 2016: Current Opinion in Microbiology
Priyanka Halder, Ranjeet Kumar, Kuladip Jana, Sohini Chakraborty, Zhumur Ghosh, Manikuntala Kundu, Joyoti Basu
Macrophages play an important role in the establishment of infection by intracellular pathogens. Mycobacterium tuberculosis is known to inhibit apoptosis and to downregulate immune responses of host cells using various strategies, including activation of peroxisome proliferator-activated receptor (PPAR)γ. Mannose-capped lipoarabinomannan (ManLAM) is one of the known bacterial effectors that plays a role in subversion of host immunity and activation of PPARγ. Here, we have used an unbiased global gene expression profiling approach to understand (a) how ManLAM regulates host cell immune responses and (b) the role of PPARγ in modulating ManLAM-induced host cell signaling...
September 2015: IUBMB Life
Kirtimaan Syal, Anand Srinivasan, Dibyajyoti Banerjee
Diabetes and tuberculosis are world's most deadly epidemics. People suffering from diabetes are susceptible to tuberculosis. Molecular link between the two is largely unknown. It is known that Vitamin A receptor (RXR) heterodimerizes with Vitamin D receptor (VDR) and Peroxisome proliferator-activator receptor-γ (PPARγ) to regulate Tryptophan-aspartate containing coat protein (TACO) expression and fatty acid metabolism respectively, so it would be interesting to check the expression of these genes in diabetes mellitus (DM) patients which might explain the susceptibility of diabetics to tuberculosis...
July 2015: Indian Journal of Clinical Biochemistry: IJCB
Stephanie Kallert, Sebastian F Zenk, Paul Walther, Mark Grieshober, Tanja Weil, Steffen Stenger
Lipoarabinomannan (LAM) is a major cell wall component of Mycobacterium tuberculosis (Mtb). LAM specific human T-lymphocytes release interferon-γ (IFNγ) and have antimicrobial activity against intracellular Mtb suggesting that they contribute to protection. Therefore the induction of LAM-specific memory T-cells is an attractive approach for the design of a new vaccine against tuberculosis. A prerequisite for the activation of LAM-specific T-cells is the efficient uptake and transport of the glycolipid antigen to the CD1 antigen presenting machinery...
July 2015: Tuberculosis
Vineet Ahuja, Swati Subodh, Amit Tuteja, Veena Mishra, Sushil Kumar Garg, Neha Gupta, Govind Makharia, S K Acharya
BACKGROUND AND AIMS: Crohn's disease (CD) and intestinal tuberculosis (ITB) are both chronic granulomatous conditions with similar phenotypic presentations. Hence, there is need for a biomarker to differentiate between both these two diseases. This study aimed at genome-wide gene expression analysis of colonic biopsies from confirmed cases of ITB and CD in comparison with controls. To evaluate the role of T regulatory cells, forkhead box P3 (FOXP3) mRNA expression was quantified in serum as well as in colonic biopsies from patients with ITB and with the controls...
February 2016: Gastroenterology Report
Li Liu, Jincheng Liu, Guoqiang Niu, Qianhong Xu, Qiliang Chen
Mycobacterium tuberculosis (M.tb) enhances its survival in macrophages by suppressing immune responses, in part through its complex cell wall structures. M.tb 19‑kDa lipoprotein (P19), a component of the complex cell wall structures of M.tb, is a Toll‑like receptor (TLR) agonist, and may induce immune responses through TLR2. Furthermore, the activation of peroxisome proliferator‑activated receptor γ (PPARγ) is also involved in M.tb‑induced immune responses in macrophages. In the present study, specific agonists/antagonists and siRNA were used to investigate the role of PPARγ in P19‑induced immune responses in human macrophages, including TLR2 activation, p38 phosphorylation and cytokine production...
April 2015: Molecular Medicine Reports
Sung-Jo Kim, Minho Hong, Ki Duk Song, Hak-Kyo Lee, Sungweon Ryoo, Tae-Hwe Heo
BACKGROUND: Tuberculosis (TB) is a respiratory tract disease caused by Mycobacterium tuberculosis infection. M. tuberculosis exploits immune privilege to grow and divide in pleural macrophages. Fibrates are associated with the immune response and control lipid metabolism through glycolysis with β-oxidation of fatty acids. RESULTS: In this study, we investigated the effect of fibrate pretreatment on the immune response during M. smegmatis infection in U937 cells, a human leukemic monocyte lymphoma cell line...
2014: Biological Research
Hugh Salamon, Natalie Bruiners, Karim Lakehal, Lanbo Shi, Janani Ravi, Ken D Yamaguchi, Richard Pine, Maria Laura Gennaro
Vitamin D has long been linked to resistance to tuberculosis, an infectious respiratory disease that is increasingly hard to treat because of multidrug resistance. Previous work established that vitamin D induces macrophage antimicrobial functions against Mycobacterium tuberculosis. In this article, we report a novel, metabolic role for vitamin D in tuberculosis identified through integrated transcriptome and mechanistic studies. Transcriptome analysis revealed an association between vitamin D receptor (VDR) and lipid metabolism in human tuberculosis and infected macrophages...
July 1, 2014: Journal of Immunology: Official Journal of the American Association of Immunologists
Jingjing Li, Izabela Gierach, Alison R Gillies, Charles D Warden, David W Wood
The peroxisome proliferator-activated receptor gamma (PPARγ or PPARG) belongs to the nuclear receptor superfamily, and is a potential drug target for a variety of diseases. In this work, we constructed a series of bacterial biosensors for the identification of functional PPARγ ligands. These sensors entail modified Escherichia coli cells carrying a four-domain fusion protein, comprised of the PPARγ ligand binding domain (LBD), an engineered mini-intein domain, the E. coli maltose binding protein (MBD), and a thymidylate synthase (TS) reporter enzyme...
November 15, 2011: Biosensors & Bioelectronics
Murugesan V S Rajaram, Michelle N Brooks, Jessica D Morris, Jordi B Torrelles, Abul K Azad, Larry S Schlesinger
Mycobacterium tuberculosis enhances its survival in macrophages by suppressing immune responses in part through its complex cell wall structures. Peroxisome proliferator-activated receptor gamma (PPARgamma), a nuclear receptor superfamily member, is a transcriptional factor that regulates inflammation and has high expression in alternatively activated alveolar macrophages and macrophage-derived foam cells, both cell types relevant to tuberculosis pathogenesis. In this study, we show that virulent M. tuberculosis and its cell wall mannose-capped lipoarabinomannan induce PPARgamma expression through a macrophage mannose receptor-dependent pathway...
July 15, 2010: Journal of Immunology: Official Journal of the American Association of Immunologists
Patrick M McDonough, Ramses M Agustin, Randall S Ingermanson, Patricia A Loy, Benjamin M Buehrer, James B Nicoll, Natalie L Prigozhina, Ivana Mikic, Jeffrey H Price
Intracellular lipid droplets are associated with a myriad of afflictions including obesity, fatty liver disease, coronary artery disease, and infectious diseases (eg, HCV and tuberculosis). To develop high-content analysis (HCA) techniques to analyze lipid droplets and associated proteins, primary human preadipocytes were plated in 96-well dishes in the presence of rosiglitazone (rosi), a PPAR-(c) agonist that promotes adipogenesis. The cells were then labeled for nuclei, lipid droplets, and proteins such as perilipin, protein kinase C (PKC), and hormone-sensitive lipase (HSL)...
October 2009: Assay and Drug Development Technologies
Patrícia E Almeida, Adriana R Silva, Clarissa M Maya-Monteiro, Dániel Töröcsik, Heloisa D'Avila, Balázs Dezsö, Kelly G Magalhães, Hugo C Castro-Faria-Neto, Laszlo Nagy, Patrícia T Bozza
Macrophages have important roles in both lipid metabolism and inflammation and are central to immunity to intracellular pathogens. Foam-like, lipid-laden macrophages are present during the course of mycobacterial infection and have recently been implicated in mycobacterial pathogenesis. In this study, we analyzed the molecular mechanisms underlying the formation of macrophage lipid bodies (lipid droplets) during Mycobacterium bovis bacillus Calmette-Guérin (BCG) infection, focusing on the role of the lipid-activated nuclear receptor peroxisome proliferator-activated receptor gamma (PPARgamma)...
July 15, 2009: Journal of Immunology: Official Journal of the American Association of Immunologists
Yael Yuhas, Eva Berent, Regev Cohen, Shai Ashkenazi
Rifampin (rifampicin), an important antibiotic agent and a major drug used for the treatment of tuberculosis, exerts immunomodulatory effects. Previous studies have found that rifampin increases inducible nitric oxide (NO) synthase (iNOS) expression and NO production. The present study investigated the potential mechanism(s) underlying these actions. The incubation of human lung epithelial A549 cells with a cytokine mix (interleukin-1beta, tumor necrosis factor alpha, and gamma interferon) induced the expression of iNOS mRNA...
April 2009: Antimicrobial Agents and Chemotherapy
Mostafa Z Badr, Alexander Shnyra, Mikhail Zoubine, Maxim Norkin, Betty Herndon, Tim Quinn, Roberto N Miranda, Michael L Cunningham, Agostino Molteni
Infection with Mycobacterium tuberculosis (TB) induces pulmonary immunopathology mediated by classical Th1 type of acquired immunity with hepatic involvement in up to 80% of disseminated cases. Since PPAR agonists cause immune responses characterized by a decrease in the secretion of Th1 cytokines, we investigated the impact of activating these receptors on hepatic pathology associated with a well-characterized model of Th1-type pulmonary response. Male Fischer 344 rats were either maintained on a drug-free diet (groups I and II), or a diet containing diethylhexylphthalate (DEHP), a compound transformed in vivo to metabolites known to activate PPARs, for 21 days (groups III and IV)...
2007: PPAR Research
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