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
Tumour ischaemia by interferon-? resembles physiological blood vessel regression.
AuthorsKammertoens T, Friese C, Arina A, Idel C, Briesemeister D, Rothe M, Ivanov A, Szymborska A, Patone G, Kunz S, Sommermeyer D, Engels B, Leisegang M, Textor A, Fehling HJ, Fruttiger M, Lohoff M, Herrmann A, Yu H, Weichselbaum R, Uckert W, Hübner N, Gerhardt H, Beule D, Schreiber H, Blankenstein T
JournalNature
PubMed ID28445461
'The relative contribution of the effector molecules produced by T cells to tumour rejection is unclear, but interferon-? (IFN?) is critical in most of the analysed models. Although IFN? can impede tumour growth by acting directly on cancer cells, it must also act on the tumour stroma for effective rejection ... More
Pre-existing Immunity to Oncolytic Virus Potentiates Its Immunotherapeutic Efficacy.
AuthorsRicca JM, Oseledchyk A, Walther T, Liu C, Mangarin L, Merghoub T, Wolchok JD, Zamarin D
JournalMol Ther
PubMed ID29478729
'Anti-viral immunity presents a major hurdle for systemically administered oncolytic viruses (OV). Intratumoral OV therapy has a potential to overcome this problem through activation of anti-tumor immune response, with local and abscopal effects. However, the effects of anti-viral immunity in such a setting are still not well defined. Using Newcastle ... 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
Development of a thermostable spray dried outer membrane vesicle pertussis vaccine for pulmonary immunization.
AuthorsKanojia G, Raeven RHM, van der Maas L, Bindels THE, van Riet E, Metz B, Soema PC, Ten Have R, Frijlink HW, Amorij JP, Kersten GFA
JournalJ Control Release
PubMed ID30048656
'Worldwide resurgence of whooping cough calls for improved, next-generation pertussis vaccines that induce broad and long-lasting immunity. A mucosal pertussis vaccine based on outer membrane vesicles (omvPV) is a promising candidate. Further, a vaccine that is stable outside the cold chain would be of substantial advantage for worldwide distribution and ... More
Exposure to air pollution interacts with obesogenic nutrition to induce tissue-specific response patterns.
AuthorsPardo M, Kuperman Y, Levin L, Rudich A, Haim Y, Schauer JJ, Chen A, Rudich Y
JournalEnviron Pollut
PubMed ID29684880
'Obesity and exposure to particular matter (PM) have become two leading global threats to public health. However, the exact mechanisms and tissue-specificity of their health effects are largely unknown. Here we investigate whether a metabolic challenge (early nutritional obesity) synergistically interacts with an environmental challenge (PM exposure) to alter genes ... More
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
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
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
A Novel Approach to Reinstating Tolerance in Experimental Autoimmune Myasthenia Gravis Using a Targeted Fusion Protein, mCTA1-T146.
AuthorsConsonni A, Sharma S, Schön K, Lebrero-Fernández C, Rinaldi E, Lycke NY, Baggi F
JournalFront Immunol
PubMed ID28959261
Reinstating tissue-specific tolerance has attracted much attention as a means to treat autoimmune diseases. However, despite promising results in rodent models of autoimmune diseases, no established tolerogenic therapy is clinically available yet. In the experimental autoimmune myasthenia gravis (EAMG) model several protocols have been reported that induce tolerance against the ... More
Polymicrobial sepsis impairs bystander recruitment of effector cells to infected skin despite optimal sensing and alarming function of skin resident memory CD8 T cells.
AuthorsDanahy DB, Anthony SM, Jensen IJ, Hartwig SM, Shan Q, Xue HH, Harty JT, Griffith TS, Badovinac VP
JournalPLoS Pathog
PubMed ID28910403
Sepsis is a systemic infection that enhances host vulnerability to secondary infections normally controlled by T cells. Using CLP sepsis model, we observed that sepsis induces apoptosis of circulating memory CD8 T-cells (TCIRCM) and diminishes their effector functions, leading to impaired CD8 T-cell mediated protection to systemic pathogen re-infection. In ... 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
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
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
Influence of Menopause on Inflammatory Cytokines during Murine and Human Bone Fracture Healing.
AuthorsFischer V, Kalbitz M, Müller-Graf F, Gebhard F, Ignatius A, Liedert A, Haffner-Luntzer M
JournalInt J Mol Sci
PubMed ID30013010
Postmenopausal females display a chronic inflammatory phenotype with higher levels of circulating pro-inflammatory cytokines. Furthermore, the inflammatory response to injury may be altered under estrogen-deficiency, because it was shown previously that estrogen-deficient mice displayed increased levels of the inflammatory cytokines Midkine (Mdk) and Interleukin-6 (IL-6) in the early fracture hematoma. ... More
GADD45ß plays a protective role in acute lung injury by regulating apoptosis in experimental sepsis in vivo.
AuthorsMoon SJ, Kim HY, Kim YH, Kim KS, Noh JR, Kim HJ, Choi JH, Hwang JH, Lee CH
JournalJ Cell Physiol
PubMed ID29741778
Sepsis is a systemic inflammatory response syndrome due to microbial infection. Growth arrest and DNA-damage-inducible 45?beta (GADD45ß) are induced by genotoxic stress and inflammatory cytokines. However, the role of GADD45ß during bacterial infection remains unclear. This study was aimed at investigating the role of GADD45ß in sepsis. We used GADD45ß-knockout ... More
Intestinal Epithelial Cell Autophagy Is Required to Protect against TNF-Induced Apoptosis during Chronic Colitis in Mice.
AuthorsPott J, Kabat AM, Maloy KJ
JournalCell Host Microbe
PubMed ID29358084
Genome-wide association studies have linked polymorphisms in the autophagy gene ATG16L1 with susceptibility to inflammatory bowel disease (IBD). However, the cell-type-specific effects of autophagy on the regulation of chronic intestinal inflammation have not been investigated. Here, we assessed the effect of myeloid-specific or intestinal epithelial cell (IEC)-specific deletion of Atg16l1 on ... 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
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