The Coagulation and Immune Systems Are Directly Linked through the Activation of Interleukin-1a by Thrombin.
AuthorsBurzynski LC, Humphry M, Pyrillou K, Wiggins KA, Chan JNE, Figg N, Kitt LL, Summers C, Tatham KC, Martin PB, Bennett MR, Clarke MCH
JournalImmunity
PubMed ID30926232
'Ancient organisms have a combined coagulation and immune system, and although links between inflammation and hemostasis exist in mammals, they are indirect and slower to act. Here we investigated direct links between mammalian immune and coagulation systems by examining cytokine proproteins for potential thrombin protease consensus sites. We found that ... More
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
Regulation of HMGB1 release protects chemoradiotherapy-associated mucositis.
AuthorsIm KI, Nam YS, Kim N, Song Y, Lee ES, Lim JY, Jeon YW, Cho SG
JournalMucosal Immunol
PubMed ID30647411
'Oral mucositis (OM) is a common complication in cancer patients undergoing anticancer treatment. Despite the clinical and economic consequences of OM, there are no drugs available for its fundamental control. Here we show that high-mobility group box 1 (HMGB1), a "danger signal" that acts as a potent innate immune mediator, ... 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
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
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
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
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
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
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
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
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
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
Gfra1 Underexpression Causes Hirschsprung's Disease and Associated Enterocolitis in Mice.
AuthorsPorokuokka LL, Virtanen HT, Lindén J, Sidorova Y, Danilova T, Lindahl M, Saarma M, Andressoo JO
JournalCell Mol Gastroenterol Hepatol
PubMed ID30594740
RET, the receptor for the glial cell line-derived neurotrophic factor (GDNF) family ligands, is the most frequently mutated gene in congenital aganglionic megacolon or Hirschsprung's disease (HSCR). The leading cause of mortality in HSCR is HSCR-associated enterocolitis (HAEC), which is characterized by altered mucin composition, mucin retention, bacterial adhesion to ... 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