Effect of freeze-dried Carica papaya leaf juice on inflammatory cytokines production during dengue virus infection in AG129 mice.
AuthorsNorahmad NA, Mohd Abd Razak MR, Mohmad Misnan N, Md Jelas NH, Sastu UR, Muhammad A, Ho TCD, Jusoh B, Zolkifli NA, Thayan R, Mat Ripen A, Zainol M, Syed Mohamed AF
JournalBMC Complement Altern Med
PubMed ID30744623
'Carica papaya leaves have been used for traditional treatment of dengue fever and have been reported to exhibit an immunomodulatory activity by affecting the level of cytokine production in vitro and in vivo. Due to the lack of adequate in vivo evidence in dengue disease model, the present study was ... More
Fasting-Mimicking Diet Modulates Microbiota and Promotes Intestinal Regeneration to Reduce Inflammatory Bowel Disease Pathology.
AuthorsRangan P, Choi I, Wei M, Navarrete G, Guen E, Brandhorst S, Enyati N, Pasia G, Maesincee D, Ocon V, Abdulridha M, Longo VD
JournalCell Rep
PubMed ID30840892
'Dietary interventions are potentially effective therapies for inflammatory bowel diseases (IBDs). We tested the effect of 4-day fasting-mimicking diet (FMD) cycles on a chronic dextran sodium sulfate (DSS)-induced murine model resulting in symptoms and pathology associated with IBD. These FMD cycles reduced intestinal inflammation, increased stem cell number, stimulated protective ... More
Loss of MAPK-activated protein kinase 2 enables potent dendritic cell-driven anti-tumour T cell response.
AuthorsSoukup K, Halfmann A, Dillinger B, Poyer F, Martin K, Blauensteiner B, Kauer M, Kuttke M, Schabbauer G, Dohnal AM
JournalSci Rep
PubMed ID28924177
'Maintaining dendritic cells (DC) in a state of dysfunction represents a key mechanism by which tumour cells evade recognition and elimination by the immune system. Limited knowledge about the intracellular mediators of DC dysfunction restricts success of therapies aimed at reactivating a DC-driven anti-tumour immune response. Using a cell type-specific ... More
Sorafenib tosylate inhibits directly necrosome complex formation and protects in mouse models of inflammation and tissue injury.
AuthorsMartens S, Jeong M, Tonnus W, Feldmann F, Hofmans S, Goossens V, Takahashi N, Bräsen JH, Lee EW, Van der Veken P, Joossens J, Augustyns K, Fulda S, Linkermann A, Song J, Vandenabeele P
JournalCell Death Dis
PubMed ID28661484
'Necroptosis contributes to the pathophysiology of several inflammatory, infectious and degenerative disorders. TNF-induced necroptosis involves activation of the receptor-interacting protein kinases 1 and 3 (RIPK1/3) in a necrosome complex, eventually leading to the phosphorylation and relocation of mixed lineage kinase domain like protein (MLKL). Using a high-content screening of small ... More
Small Heterodimer Partner Deficiency Increases Inflammatory Liver Injury Through C-X-C motif chemokine ligand 2-Driven Neutrophil Recruitment in Mice.
AuthorsNoh JR, Kim YH, Kim DK, Hwang JH, Kim KS, Choi DH, Lee SJ, Lee HG, Lee TG, Weng HL, Dooley S, Choi HS, Lee CH
JournalToxicol Sci
PubMed ID29409050
'Although detailed pathophysiological mechanisms of fulminant hepatitis remain elusive, immune cell recruitment with excessive cytokine production is a well-recognized hallmark of the disease. We determined the function of orphan nuclear receptor small heterodimer partner (SHP) in concanavalin A (ConA)-induced hepatitis model. Male C57BL/6 J mice were injected intravenously with either ... More
Design, synthesis and evaluation of (
AuthorsChough C, Lee S, Joung M, Lee J, Kim JH, Kim BM
JournalMedchemcomm
PubMed ID30108938
'Based on ('
Dual Inhibition of PI3K/Akt and mTOR by the Dietary Antioxidant, Delphinidin, Ameliorates Psoriatic Features In Vitro and in an Imiquimod-Induced Psoriasis-Like Disease in Mice.
AuthorsChamcheu JC, Adhami VM, Esnault S, Sechi M, Siddiqui IA, Satyshur KA, Syed DN, Dodwad SM, Chaves-Rodriquez MI, Longley BJ, Wood GS, Mukhtar H
JournalAntioxid Redox Signal
PubMed ID27393705
'The treatment of psoriasis remains elusive, underscoring the need for identifying novel disease targets and mechanism-based therapeutic approaches. We recently reported that the PI3K/Akt/mTOR pathway that is frequently deregulated in many malignancies is also clinically relevant for psoriasis. We also provided rationale for developing delphinidin (Del), a dietary antioxidant for ... More
Ventilator-induced lung injury is aggravated by antibiotic mediated microbiota depletion in mice.
AuthorsWienhold SM, Macrì M, Nouailles G, Dietert K, Gurtner C, Gruber AD, Heimesaat MM, Lienau J, Schumacher F, Kleuser B, Opitz B, Suttorp N, Witzenrath M, Müller-Redetzky HC
JournalCrit Care
PubMed ID30373626
'Antibiotic exposure alters the microbiota, which can impact the inflammatory immune responses. Critically ill patients frequently receive antibiotic treatment and are often subjected to mechanical ventilation, which may induce local and systemic inflammatory responses and development of ventilator-induced lung injury (VILI). The aim of this study was to investigate whether ... More
Tsr Chemoreceptor Interacts With IL-8 Provoking E. coli Transmigration Across Human Lung Epithelial Cells.
AuthorsHan B, Li M, Xu Y, Islam D, Khang J, Del Sorbo L, Lee W, Szaszi K, Zhong N, Slutsky AS, Li Y, Zhang H
JournalSci Rep
PubMed ID27506372
'Bacterial colonization of epithelial surfaces and subsequent transmigration across the mucosal barrier are essential for the development of infection. We hypothesized that the methyl-accepting proteins (MCPs), known as chemoreceptors expressed on Escherichia coli (E. coli) bacterial surface, play an important role in mediating bacterial transmigration. We demonstrated a direct interaction ... More
SCD1 mediates the influence of exogenous saturated and monounsaturated fatty acids in adipocytes: Effects on cellular stress, inflammatory markers and fatty acid elongation.
AuthorsRalston JC, Metherel AH, Stark KD, Mutch DM
JournalJ Nutr Biochem
PubMed ID26481476
'Palmitate (PA), stearate (SA), palmitoleate (PMA) and oleate (OA) are among the most abundant fatty acids (FAs) in adipose tissue (AT). These FAs differentially regulate AT inflammation by altering adipocyte signalling pathways and the secretion of proinflammatory cytokines. Intracellular levels of these FAs are controlled, in part, by stearoyl-CoA desaturase ... More
Anti-inflammatory and anti-chemotactic effects of dietary flaxseed oil on CD8(+) T cell/adipocyte-mediated cross-talk.
AuthorsMonk JM, Liddle DM, Brown MJ, Zarepoor L, De Boer AA, Ma DW, Power KA, Robinson LE
JournalMol Nutr Food Res
PubMed ID26616354
CD8(+) T cell/adipocyte paracrine interactions represent a critical step in the development of the obese inflammatory phenotype that is disrupted by long-chain n-3 PUFA. Our objective was to determine the effect of flaxseed-derived n-3 PUFA (a-linolenic acid) on these paracrine interactions. ... More
Safety Assessment of Bacteroides uniformis CECT 7771 Isolated from Stools of Healthy Breast-Fed Infants.
AuthorsFernández-Murga ML, Sanz Y
JournalPLoS One
PubMed ID26784747
Bacteroides uniformis CECT 7771 is a potential probiotic strain, originally isolated from the stools of healthy breast-feed infants. The strain showed pre-clinical efficacy in a mouse obesity model. The objective of this study was to evaluate its potential toxicity and translocation ability after acute oral administration to mice. ... More
The delta 6 desaturase knock out mouse reveals that immunomodulatory effects of essential n-6 and n-3 polyunsaturated fatty acids are both independent of and dependent upon conversion.
AuthorsMonk JM, Liddle DM, Cohen DJ, Tsang DH, Hillyer LM, Abdelmagid SA, Nakamura MT, Power KA, Ma DW, Robinson LE
JournalJ Nutr Biochem
PubMed ID27142734
Typically fatty acids (FA) exert differential immunomodulatory effects with n-3 [a-linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] and n-6 [linoleic acid (LA) and arachidonic acid (AA)] exerting anti- and pro-inflammatory effects, respectively. This over-simplified interpretation is confounded by a failure to account for conversion of the parent ... More
Fish-oil-derived n-3 polyunsaturated fatty acids reduce NLRP3 inflammasome activity and obesity-related inflammatory cross-talk between adipocytes and CD11b(+) macrophages.
AuthorsDe Boer AA, Monk JM, Liddle DM, Hutchinson AL, Power KA, Ma DW, Robinson LE
JournalJ Nutr Biochem
PubMed ID27208584
Adipocyte-macrophage cross-talk propagates immune responses in obese adipose tissue (AT). Long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) mitigate inflammation, partly through up-regulation of adiponectin; however, specific mechanisms are unclear. We determined if adipocyte-macrophage cross-talk could be mitigated by dietary LC n-3 PUFA and if this was dependent on adiponectin-mediated ... More
The impact of ranitidine on monocyte responses in the context of solid tumors.
AuthorsVila-Leahey A, Rogers D, Marshall JS
JournalOncotarget
PubMed ID26863636
Monocytes and myeloid derived suppressor cells (MDSC) have been implicated on the regulation of tumor growth. Histamine is also important for regulating MDSC responses. Oral administration of the H2 receptor antagonist ranitidine can inhibit breast tumor growth and metastasis. In the current study, we examined the impact of oral ranitidine ... More
AuthorsJaimes Y, Naaldijk Y, Wenk K, Leovsky C, Emmrich F
JournalStem Cells
PubMed ID27862694
Microglia cells are the central nervous system immune cells and have been pointed out as the main mediators of the inflammation leading to neurodegenerative disorders. Mesenchymal stromal cells (MSCs) are a heterogeneous population of cells with very high self-renewal properties and uncomplicated in vitro culture. Research has shown that MSCs ... More
Alteration of Gut Microbiota and Inflammatory Cytokine/Chemokine Profiles in 5-Fluorouracil Induced Intestinal Mucositis.
AuthorsLi HL, Lu L, Wang XS, Qin LY, Wang P, Qiu SP, Wu H, Huang F, Zhang BB, Shi HL, Wu XJ
JournalFront Cell Infect Microbiol
PubMed ID29124041
Disturbed homeostasis of gut microbiota has been suggested to be closely associated with 5-fluorouracil (5-Fu) induced mucositis. However, current knowledge of the overall profiles of 5-Fu-disturbed gut microbiota is limited, and so far there is no direct convincing evidence proving the causality between 5-Fu-disturbed microbiota and colonic mucositis. In mice, ... More
Pregnancy-Related Immune Adaptation Promotes the Emergence of Highly Virulent H1N1 Influenza Virus Strains in Allogenically Pregnant Mice.
AuthorsEngels G, Hierweger AM, Hoffmann J, Thieme R, Thiele S, Bertram S, Dreier C, Resa-Infante P, Jacobsen H, Thiele K, Alawi M, Indenbirken D, Grundhoff A, Siebels S, Fischer N, Stojanovska V, Muzzio D, Jensen F, Karimi K, Mittrücker HW, Arck PC, Gabriel G
JournalCell Host Microbe
PubMed ID28279344
Pregnant women are at high risk for severe influenza disease outcomes, yet insights into the underlying mechanisms are limited. Here, we present models of H1N1 infection in syngenic and allogenic pregnant mice; infection in the latter mirrors the severe course of 2009 pandemic influenza in pregnant women. We found that ... More
Expanding biological activities of Ts19 Frag-II toxin: Insights into IL-17 production.
Tityus serrulatus (Ts) venom is composed of a mixture of toxins presenting diverse biological functions. However, although this venom has been studied over the past three decades, omics analysis revealed that most of its toxins are not identified or their biological activities are unknown. Ts19 Frag-II is included in this ... More
The Stimulation of Macrophages with TLR Ligands Supports Increased IL-19 Expression in Inflammatory Bowel Disease Patients and in Colitis Models.
AuthorsSteinert A, Linas I, Kaya B, Ibrahim M, Schlitzer A, Hruz P, Radulovic K, Terracciano L, Macpherson AJ, Niess JH
JournalJ Immunol
PubMed ID28864472
IL-19, a member of the IL-10 cytokine family that signals through the IL-20 receptor type I (IL-20Ra:IL-20Rß), is a cytokine whose function is not completely known. In this article, we show that the expression of ... More
XIAP Loss Triggers RIPK3- and Caspase-8-Driven IL-1ß Activation and Cell Death as a Consequence of TLR-MyD88-Induced cIAP1-TRAF2 Degradation.
AuthorsLawlor KE, Feltham R, Yabal M, Conos SA, Chen KW, Ziehe S, Graß C, Zhan Y, Nguyen TA, Hall C, Vince AJ, Chatfield SM, D'Silva DB, Pang KC, Schroder K, Silke J, Vaux DL, Jost PJ, Vince JE
JournalCell Rep
PubMed ID28723569
X-linked Inhibitor of Apoptosis (XIAP) deficiency predisposes people to pathogen-associated hyperinflammation. Upon XIAP loss, Toll-like receptor (TLR) ligation triggers RIPK3-caspase-8-mediated IL-1ß activation and death in myeloid cells. How XIAP suppresses these events remains unclear. Here, we show that TLR-MyD88 causes the proteasomal degradation of the related IAP, cIAP1, and its ... More
Gelatinase B/matrix metalloproteinase-9 is a phase-specific effector molecule, independent from Fas, in experimental autoimmune encephalomyelitis.
AuthorsUgarte-Berzal E, Berghmans N, Boon L, Martens E, Vandooren J, Cauwe B, Thijs G, Proost P, Van Damme J, Opdenakker G
JournalPLoS One
PubMed ID30273366
Gelatinase B/matrix metalloproteinase-9 (MMP-9) triggers multiple sclerosis (MS) and the animal model of experimental autoimmune encephalomyelitis (EAE) by the breakdown of the blood-brain barrier. Interestingly, MMP-9 is beneficial in systemic autoimmunity caused by Fas-deficiency. Fas-deficient (faslpr) and Fas-ligand-deficient mice are protected against EAE. We here investigated the interaction between Fas ... More
Delay in antibiotic therapy results in fatal disease outcome in murine pneumococcal pneumonia.
AuthorsBerger S, Goekeri C, Gupta SK, Vera J, Dietert K, Behrendt U, Lienau J, Wienhold SM, Gruber AD, Suttorp N, Witzenrath M, Nouailles G
JournalCrit Care
PubMed ID30382866
Community-acquired pneumonia (CAP) remains a major cause of death worldwide. Mechanisms underlying the detrimental outcome despite adequate antibiotic therapy and comorbidity management are still not fully understood. ... More
Sortase A as a cross-linking enzyme in tissue engineering.
AuthorsBroguiere N, Formica FA, Barreto G, Zenobi-Wong M
JournalActa Biomater
PubMed ID30006315
The bacterial ligase Sortase A (SA) and its mutated variants have become increasingly popular over the last years for post-translational protein modifications due to their unparalleled specificity and efficiency. The aim of this work was to study SA as a cross-linking enzyme for hydrogel-based tissue engineering. For this, we optimized ... More
Western Diet Triggers NLRP3-Dependent Innate Immune Reprogramming.
AuthorsChrist A, Günther P, Lauterbach MAR, Duewell P, Biswas D, Pelka K, Scholz CJ, Oosting M, Haendler K, Baßler K, Klee K, Schulte-Schrepping J, Ulas T, Moorlag SJCFM, Kumar V, Park MH, Joosten LAB, Groh LA, Riksen NP, Espevik T, Schlitzer A, Li Y, Fitzgerald ML, Netea MG, Schultze JL, Latz E
JournalCell
PubMed ID29328911
Long-term epigenetic reprogramming of innate immune cells in response to microbes, also termed "trained immunity," causes prolonged altered cellular functionality to protect from secondary infections. Here, we investigated whether sterile triggers of inflammation induce trained immunity and thereby influence innate immune responses. Western diet (WD) feeding of Ldlr ... More
Development of selective inhibitors for the treatment of rheumatoid arthritis: (R)-3-(3-(Methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)pyrrolidin-1-yl)-3-oxopropanenitrile as a JAK1-selective inhibitor.
AuthorsChough C, Joung M, Lee S, Lee J, Kim JH, Kim BM
JournalBioorg Med Chem
PubMed ID29452839
A series of 3(R)-aminopyrrolidine derivatives were designed and synthesized for JAK1-selective inhibitors through the modification of tofacitinib's core structure, (3R,4R)-3-amino-4-methylpiperidine. From the new core structures, we selected (R)-N-methyl-N-(pyrrolidin-3-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine as a scaffold for further SAR studies. From biochemical enzyme assays and liver microsomal stability tests, (R)-3-(3-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)pyrrolidin-1-yl)-3-oxopropanenitrile (6) was chosen for further ... More
3D Organotypic Spinal Cultures: Exploring Neuron and Neuroglia Responses Upon Prolonged Exposure to Graphene Oxide.
AuthorsMusto M, Rauti R, Rodrigues AF, Bonechi E, Ballerini C, Kostarelos K, Ballerini L
JournalFront Syst Neurosci
PubMed ID30733671
Graphene-based nanomaterials are increasingly engineered as components of biosensors, interfaces or drug delivery platforms in neuro-repair strategies. In these developments, the mostly used derivative of graphene is graphene oxide (GO). To tailor the safe development of GO nanosheets, we need to model ... More
Post-transplantation cyclophosphamide prevents graft-versus-host disease by inducing alloreactive T cell dysfunction and suppression.
Post-transplantation cyclophosphamide (PTCy) recently has had a marked impact on human allogeneic hematopoietic cell transplantation (HCT). Yet, our understanding of how PTCy prevents graft-versus-host disease (GVHD) largely has been extrapolated from major histocompatibility complex (MHC)-matched murine skin allografting models that were highly contextual in their efficacy. Herein, we developed a ... More
The ATG5-binding and coiled coil domains of ATG16L1 maintain autophagy and tissue homeostasis in mice independently of the WD domain required for LC3-associated phagocytosis.
AuthorsRai S, Arasteh M, Jefferson M, Pearson T, Wang Y, Zhang W, Bicsak B, Divekar D, Powell PP, Naumann R, Beraza N, Carding SR, Florey O, Mayer U, Wileman T
JournalAutophagy
PubMed ID30403914
Macroautophagy/autophagy delivers damaged proteins and organelles to lysosomes for degradation, and plays important roles in maintaining tissue homeostasis by reducing tissue damage. The translocation of LC3 to the limiting membrane of the phagophore, the precursor to the autophagosome, during autophagy provides a binding site for autophagy cargoes, and facilitates fusion ... More
Global proteomic and functional analysis of Crotalus durissus collilineatus individual venom variation and its impact on envenoming.
Individual variations studies are important to understand the snakebite envenoming and to improve the antivenom production and its effectiveness. In this way, the objective of this study was a comparative analysis of intraspecific variation in the venom composition of 22 Crotalus durissus collilineatus specimens through proteomic techniques. Venoms were fractionated ... More
Reduced Terminal Complement Complex Formation in Mice Manifests in Low Bone Mass and Impaired Fracture Healing.
AuthorsMödinger Y, Rapp AE, Vikman A, Ren Z, Fischer V, Bergdolt S, Haffner-Luntzer M, Song WC, Lambris JD, Huber-Lang M, Neidlinger-Wilke C, Brenner RE, Ignatius A
JournalAm J Pathol
PubMed ID30339839
The terminal complement complex (TCC) is formed on activation of the complement system, a crucial arm of innate immunity. TCC formation on cell membranes results in a transmembrane pore leading to cell lysis. In addition, sublytic TCC concentrations can modulate various cellular functions. TCC-induced effects may play a role in ... More
Disruption of type I interferon signaling causes sexually dimorphic dysregulation of anti-viral cytokines.
Type I interferons (IFNs) play a crucial role in the establishment of an antiviral state via signaling through their cognate type I IFN receptor (IFNAR). In this study, a replication-competent but highly attenuated strain of VSV (rVSV?m51) carrying a deletion at position 51 of the matrix protein to remove suppression ... More