29 results found
de la Roche M, Hamilton C, Mortensen R, et al., 2018, Trafficking of cholesterol to the ER is required for NLRP3 inflammasome activation., J Cell Biol
Cellular lipids determine membrane integrity and fluidity and are being increasingly recognized to influence immune responses. Cellular cholesterol requirements are fulfilled through biosynthesis and uptake programs. In an intricate pathway involving the lysosomal cholesterol transporter NPC1, the sterol gets unequally distributed across intracellular compartments. By using pharmacological and genetic approaches targeting NPC1, we reveal that blockade of cholesterol trafficking through the late endosome-lysosome pathway blunts NLRP3 inflammasome activation. Altered cholesterol localization at the plasma membrane (PM) in Npc1-/- cells abrogated AKT-mTOR signaling by TLR4. However, the inability to activate the NLRP3 inflammasome was traced to perturbed cholesterol trafficking to the ER but not the PM. Accordingly, acute cholesterol depletion in the ER membranes by statins abrogated casp-1 activation and IL-1β secretion and ablated NLRP3 inflammasome assembly. By contrast, assembly and activation of the AIM2 inflammasome progressed unrestricted. Together, this study reveals ER sterol levels as a metabolic rheostat for the activation of the NLRP3 inflammasome.
Hamilton C, Tan L, Miethke T, et al., 2017, Immunity to uropathogens: the emerging roles of inflammasomes, NATURE REVIEWS UROLOGY, Vol: 14, Pages: 284-+, ISSN: 1759-4812
Lupfer C, Anand PK, 2016, Integrating Inflammasome Signaling in Sexually Transmitted Infections, TRENDS IN IMMUNOLOGY, Vol: 37, Pages: 703-714, ISSN: 1471-4906
Gurung P, Anand PK, Malireddi RKS, et al., 2014, FADD and Caspase-8 Mediate Priming and Activation of the Canonical and Noncanonical Nlrp3 Inflammasomes, JOURNAL OF IMMUNOLOGY, Vol: 192, Pages: 1835-1846, ISSN: 0022-1767
Lupfer CR, Anand PK, Liu Z, et al., 2014, Reactive Oxygen Species Regulate Caspase-11 Expression and Activation of the Non-canonical NLRP3 Inflammasome during Enteric Pathogen Infection, PLOS PATHOGENS, Vol: 10, ISSN: 1553-7366
Anand PK, Kanneganti T-D, 2013, NLRP6 in infection and inflammation, MICROBES AND INFECTION, Vol: 15, Pages: 661-668, ISSN: 1286-4579
Buffen K, Oosting M, Mennens S, et al., 2013, Autophagy Modulates Borrelia burgdorferi-induced Production of Interleukin-1 beta (IL-1 beta), JOURNAL OF BIOLOGICAL CHEMISTRY, Vol: 288, Pages: 8658-8666, ISSN: 0021-9258
Lupfer C, Thomas PG, Anand PK, et al., 2013, Receptor interacting protein kinase 2-mediated mitophagy regulates inflammasome activation during virus infection, NATURE IMMUNOLOGY, Vol: 14, Pages: 480-+, ISSN: 1529-2908
Anand PK, Kanneganti T-D, 2012, Targeting NLRP6 to enhance immunity against bacterial infections, FUTURE MICROBIOLOGY, Vol: 7, Pages: 1239-1242, ISSN: 1746-0913
Anand PK, Malireddi RKS, Lukens JR, et al., 2012, NLRP6 negatively regulates innate immunity and host defence against bacterial pathogens, NATURE, Vol: 488, Pages: 389-+, ISSN: 0028-0836
Gurung P, Malireddi RKS, Anand PK, et al., 2012, Toll or Interleukin-1 Receptor (TIR) Domain-containing Adaptor Inducing Interferon-beta (TRIF)-mediated Caspase-11 Protease Production Integrates Toll-like Receptor 4 (TLR4) Protein- and Nlrp3 Inflammasome-mediated Host Defense against Enteropathogens, JOURNAL OF BIOLOGICAL CHEMISTRY, Vol: 287, Pages: 34474-34483, ISSN: 0021-9258
Anand PK, Malireddi RKS, Kanneganti T-D, 2011, Role of the Nlrp3 inflammasome in microbial infection, FRONTIERS IN MICROBIOLOGY, Vol: 2, ISSN: 1664-302X
Anand PK, Tait SWG, Lamkanfi M, et al., 2011, TLR2 and RIP2 Pathways Mediate Autophagy of Listeria monocytogenes via Extracellular Signal-regulated Kinase (ERK) Activation, JOURNAL OF BIOLOGICAL CHEMISTRY, Vol: 286, Pages: 42981-42991, ISSN: 0021-9258
Zaki MH, Vogel P, Malireddi RKS, et al., 2011, The NOD-Like Receptor NLRP12 Attenuates Colon Inflammation and Tumorigenesis, CANCER CELL, Vol: 20, Pages: 649-660, ISSN: 1535-6108
Anand PK, 2010, Exosomal membrane molecules are potent immune response modulators., Commun Integr Biol, Vol: 3, Pages: 405-408
Exosomes are endosome-derived vesicles (40-100 nm) formed during the formation of multi-vesicular bodies (MVBs). Occasionally, the MVBs fuse with the plasma membrane releasing their intra-luminal vesicles into the extracellular media, which are then known as exosomes. Different cell types such as B-cells, dendritic cells, platelets, reticulocytes and macrophages can release exosomes and current research in this area is more focused towards exosomes released by antigen-presenting cells. Exosomes have recently been shown to be immunomodulatory and the mechanism of immune response initiation by them is beginning to emerge. Besides molecules present inside the lumen of exosomes, it has been suggested that certain exosomal membrane molecules can interact with their surface receptors on the target cells thereby inducing an immunomodulatory response. In this review, Hsp70 and galectin-5, two immunogenic molecules present on exosomal membrane, are discussed in detail for initiating this response.
Anand PK, Anand E, Bleck CKE, et al., 2010, Exosomal Hsp70 Induces a Pro-Inflammatory Response to Foreign Particles Including Mycobacteria, PLOS ONE, Vol: 5, ISSN: 1932-6203
Hoffmann E, Marion S, Mishra BB, et al., 2010, Initial receptor-ligand interactions modulate gene expression and phagosomal properties during both early and late stages of phagocytosis, EUROPEAN JOURNAL OF CELL BIOLOGY, Vol: 89, Pages: 693-704, ISSN: 0171-9335
Kuehnel MP, Reiss M, Anand PK, et al., 2009, Sphingosine-1-phosphate receptors stimulate macrophage plasma-membrane actin assembly via ADP release, ATP synthesis and P2X7R activation, JOURNAL OF CELL SCIENCE, Vol: 122, Pages: 505-512, ISSN: 0021-9533
Kuehnel MP, Rybin V, Anand PK, et al., 2009, Lipids regulate P2X7-receptor-dependent actin assembly by phagosomes via ADP translocation and ATP synthesis in the phagosome lumen, JOURNAL OF CELL SCIENCE, Vol: 122, Pages: 499-504, ISSN: 0021-9533
Anand PK, Kaul D, Sharma M, 2008, Synergistic action of vitamin D and retinoic acid restricts invasion of macrophages by pathogenic mycobacteria, JOURNAL OF MICROBIOLOGY IMMUNOLOGY AND INFECTION, Vol: 41, Pages: 17-25, ISSN: 1684-1182
Anand PK, Kaul D, Sharma M, 2006, Green tea polyphenol inhibits Mycobacterium tuberculosis survival within human macrophages., Int J Biochem Cell Biol, Vol: 38, Pages: 600-609, ISSN: 1357-2725
Lack of maturation of phagosomes containing pathogenic Mycobacterium tuberculosis within macrophages has been widely recognized as a crucial factor for the persistence of mycobacterial pathogen. Host molecule tryptophan-aspartate containing coat protein (TACO) has been shown to play a crucial role in the arrest of such a maturation process. The present study was addressed to understand whether or not polyphenols derived from green tea could down-regulate TACO gene transcription. And if yes, what impact TACO gene down-regulation has on the uptake/survival of M. tuberculosis within macrophages. The reverse-transcriptase polymerase chain reaction and reporter assay technology, employed in this study, revealed that the major component of green tea polyphenols, epigallocatechin-3-gallate had the inherent capacity to down-regulate TACO gene transcription within human macrophages through its ability to inhibit Sp1 transcription factor. We also found out that TACO gene promoter does contain Sp1 binding sequence using bioinformatics tools. The down-regulation of TACO gene expression by epigallocatechin-3-gallate was accompanied by inhibition of mycobacterium survival within macrophages as assessed through flow cytometry and colony counts. Based on these results, we propose that epigallocatechin-3-gallate may be of importance in the prevention of tuberculosis infection.
Chaudhry A, Anand PK, Singh GS, et al., 2006, Ectopic pairing of the intercalary heterochromatin in the organophosphate pesticide treated mosquito chromosomes (Culcidae: Diptera), Cytologia, Vol: 71, Pages: 431-437, ISSN: 0011-4545
The extensive use of chemical pesticides has greatly increased the mutational load on the genome of living organisms. The problems of genetic toxicology have generated more concern than any other problem because the residual inclusion of pesticides in the environment leads to a number of direct and indirect effects on the genetic material. Induced chromosomal mutations provide a reliable index of the mutagenic potential of a chemical or a physical agent. Experience has shown that the mutagenic effect of the semilethal doses of chemicals induce a of variety of structural changes in the polytene chromosomes out of which ectopic pairings are the most frequent types of aberrations. As a consequence of these points of genetic interest, the present paper deals with the incidence of ectopic pairing of the intercalary heterochromatic bands in the polytene chromosomes of those larvae of Anopheles subpictus, which were treated with LC20of 4 organophosphate pesticides viz. chlorpyrifos, monocrotophos, acephate and dimethoate. When compared with the data of non-treated controls the treated larvae had an elevated incidence of intercalary heterchromatic linkages in the X-chromosome and the right and left arms of autosomes 2 and 3 (2R, 2L, 3R, 3L). The results are discussed in relevance to the fact that ectopic associations are established between those heterochromatic bands which are homologous in their chemical and genetic properties. These properties are attributed to the presence of identical A : T rich nucleotide sequences resulting from gene duplications which are induced by the cellular environments altered by the pesticides. © 2006 The Japan Mendel Society.
Kaul D, Anand PK, Khanna A, 2006, Functional genomics of PPAR-gamma in human immunomodulatory cells, MOLECULAR AND CELLULAR BIOCHEMISTRY, Vol: 290, Pages: 211-215, ISSN: 0300-8177
Chaudhry A, Anand PK, 2005, Evaluation of the mutagenic potential of chlorpyrifos (CPF) using polytene chromosomes of Anopheles mosquito., J Environ Biol, Vol: 26, Pages: 145-150, ISSN: 0254-8704
Diverse cytogenetic tests are employed for short term screening of suspect environmental mutagens by using insects and mammals as models. In the present paper the polytene chromosomes of a mosquito Anopheles maculatus were used to evaluate the mutagenic potential of a widely used organophosphate pesticide chlorpyrifos-[o, o-diethyl-o-(3, 5, 6-trichloro-2-pyridyl) phosphothioate]. The results are based on the frequency of various structural aberrations encountered in the polytene chromosomes of the larvae treated with LC20 of chlorpyrifos (CPF). These aberrations were dominated by inversions, stickiness of the chromosomes, heterochromatinization of the bands and lack of polyteny. The frequency of various aberrations was highest in the left arm of chromosome number 2L followed by 2R, 3L, 3R, and X-chromosomes i.e. 2.10 +/- 0.44, 1.84 +/- 0.44, 1.57 +/- 0.54, 1.31 +/- 0.50, and 0.22 +/- 0.27 respectively. The susceptibility of different chromosomal arms to this pesticide was 2L > 2R > 3L > 3R > X and the regions prone to these aberrations have been marked on the polytene chromosome map of Anopheles maculatus.
Chaudhry A, Anand PK, 2004, Assessment of dominant lethal effects of chlorpyrifos (CPF) using mosquito genetics, Pollution Research, Vol: 23, Pages: 767-771, ISSN: 0257-8050
The screening of pesticides to assess their genotoxic potential using suitable experimental models and protocols is an important research activity in the area of genetic toxicology. The submammalian models like insects are most ideal for testing the dominant lethal effects of suspected environmental mutagens. The present paper deals with the results of dominant lethal tests (DLT) of a pesticide chlorpyrifos (CPF) on Culex quinquefaciatus. Males originating from larvae treated with LC20were crossed with normal females and the number of hatched and unhatched eggs was statistically analyzed. The results show CPF induced dominant lethality which led to the production of unhatched eggs. It was also observed that this pesticide is harmful to the genome for the mosquito as it produced structural and numerical aberrations in the chromosomes of male meiosis and structural alterations in the larval polytene chromosomes. Copyright © Enviromedia.
Anand PK, Kaul D, 2003, Vitamin D3-dependent pathway regulates TACO gene transcription., Biochem Biophys Res Commun, Vol: 310, Pages: 876-877, ISSN: 0006-291X
Recently, gene coding for tryptophan-aspartate containing coat protein (TACO) has been recognized to play a crucial role in the survival of Mycobacterium tuberculosis within human macrophages. Since regulation of TACO gene is still poorly understood, the present study was addressed to explore the role of vitamins (A, C, D, and E) in TACO gene transcription. Such a study revealed that synergistic action of vitamin D(3) and retinoic acid (RA) had inherent ability to down-regulate TACO gene transcription in human macrophages. Based upon these results, we propose that synergistic action of RA+vitamin D may be of importance in the prevention/control of M. tuberculosis infection.
Kaul D, Anand PK, 2003, Regulation of PPAR-gamma gene in human promyelocytic HL-60 cell line, LEUKEMIA RESEARCH, Vol: 27, Pages: 683-686, ISSN: 0145-2126
Kaul D, Anand PK, 2003, Receptor-C<inf>k</inf>regulates HMGCoA reductase gene in HL-60 cells, Current Science, Vol: 85, Pages: 643-645, ISSN: 0011-3891
Using human promyelocytic leukaemic HL-60 cell line as an archetype model, the present study was addressed to understand the role of Receptor-Ckin the modulation of sterol-response element (SRE) having DR-3 locus in the promoter region of HMGCoA reductase gene. Such a study unambiguously revealed that Receptor-Ckhas the inherent capacity to regulate this SRE sequence in HL-60 cells. Based upon this study as well as our earlier findings, it is proposed that Receptor-Ck-dependent signalling may be of importance in leukaemogenesis.
Anand PK, Kaul D, 2002, Oxysterol receptor LXR alpha regulates SREBP gene expression in HL-60 cells exposed to differentiating agents, CURRENT SCIENCE, Vol: 82, Pages: 136-137, ISSN: 0011-3891
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