Role of p38 MAPK in LPS induced pro-inflammatory cytokine and chemokine gene expression in equine leukocytes

Neuder, Laura E.; Keener, Jamie M.; Eckert, Rachael E.; Trujillo, Jennifer C.; Jones, Samuel L.

doi:10.1016/j.vetimm.2008.11.006

Cited by 66 publications

(44 citation statements)

References 49 publications

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“…Our findings provide evidence that several signaling pathways are differentially induced by neisserial LOS to tolerize human monocytes. One of the pathways, the p38 MAPK pathway, mediates many of the proinflammatory events that are induced by LPS stimulation (39)(40)(41). In particular, TNF-a and IL1-b expression is partly regulated by p38 MAPK, which posttranscriptionally stabilizes their mRNA, and a reduction in their expression is characteristic of endotoxin tolerance induced by LPS rechallenge (34,35).…”

Section: Discussionmentioning

confidence: 99%

Induction of Endotoxin Tolerance by Pathogenic Neisseria Is Correlated with the Inflammatory Potential of Lipooligosaccharides and Regulated by MicroRNA-146a

John

Jarvis

2014

The Journal of Immunology

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In this article, we report that retreatment of human monocytic THP-1 cells and primary monocytes with pathogenic Neisseria or with purified lipooligosaccharides (LOS) after previous exposure to LOS induced immune tolerance, as evidenced by reduced TNF-α and IL-1β cytokine expression. LOS that we have previously shown to vary in their potential to activate TLR4 signaling, which was correlated with differences in levels of lipid A phosphorylation, had similarly variable ability to induce tolerance. Efficacy for induction of tolerance was proportional to the level of lipid A phosphorylation, as LOS from meningococcal strain 89I with the highest degree of phosphorylation was the most tolerogenic following retreatment with LOS or whole bacteria, compared with LOS from gonococcal strains 1291 and GC56 with reduced levels of phosphorylation. Hydrogen fluoride treatment of 89I LOS to remove phosphates rendered the LOS nontolerogenic. Tolerance induced by the more highly inflammatory meningococcal LOS was correlated with significantly greater downregulation of p38 activation, greater induction of the expression of A20 and of microRNA-146a, and greater reductions in IL-1R–associated kinase 1 and TRAF6 levels following LOS retreatment of cells. The role of miR-146a in regulation of induction of TNF-α was confirmed by transfecting cells with an inhibitor and a mimic of miR-146a. Our results provide a mechanistic framework for understanding the variable pathophysiology of meningococcal and gonococcal infections given that after an initial exposure, greater upregulation of microRNA-146a by more highly inflammatory LOS conversely leads to the suppression of immune responses, which would be expected to facilitate bacterial survival and dissemination.

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Section: Discussionmentioning

confidence: 99%

Induction of Endotoxin Tolerance by Pathogenic Neisseria Is Correlated with the Inflammatory Potential of Lipooligosaccharides and Regulated by MicroRNA-146a

John

Jarvis

2014

The Journal of Immunology

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“…The p38 MAPK pathway is a member of MAPK signal transduction pathway in the cellular downstream cascade of induction of pro-inflammatory cytokine production after LPS exposure. SB203580 and SB202190 are specific p38 MAPK inhibitors and decrease protein and mRNA expression of COX-2 in LPS-stimulated equine leukocytes (Neuder et al 2009). In an in vitro experiment, equine PBMCs were treated with SB203580 or SB202190 and then exposed to LPS (10 ng/ml) (E. coli O55:B5) for 2 or 4 hours.…”

Section: Nonsteroidal Anti-inflammatory Drugs (Nsaids) Nonsteroidal mentioning

confidence: 99%

Induction and characterization of endotoxin tolerance in equine peripheral blood mononuclear cells in vitro

Frellstedt

McKenzie

Barrett

et al. 2012

Veterinary Immunology and Immunopathology

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Endotoxemia is responsible for severe illness in horses. Individuals can become unresponsive to the endotoxin molecule after an initial exposure; this phenomenon has been called developing a state of 'endotoxin tolerance' (ET). ET has been induced in horses in vivo; however, cytokine expression associated with ET has not been investigated. The purpose of this study was to develop and validate a method for inducing ET in equine peripheral blood mononuclear cells (PBMCs) in vitro, and to describe the cytokine profile which is associated with the ET.Blood was collected from 6 healthy horses and PBMCs were isolated. ET was induced by culturing cells with three concentrations of endotoxin given to induce ET, and evaluated after a second dose of endotoxin given to challenge the cells. The relative mRNA expression of IL-10 and IL-12 was measured by use of quantitative PCR.ET was induced in all cells (n=6) exposed to the 2-step endotoxin challenge. In PBMCs treated with 1.0 ng/ml of endotoxin followed by challenge with 10 ng/ml of endotoxin, the relative mRNA expression of IL-10 in tolerized cells was not different from positive control cells. In contrast, the relative mRNA expression of IL-12 in tolerized cells was decreased by 15-fold after the second endotoxin challenge compared with positive control cells.This experiment demonstrated a reliable method for the ex vivo induction of ET in equine PBMCs. A marked suppression of IL-12 production is associated with ET. The production of IL-10 was not altered in ET in our model.

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“…IL-8 também tem sido implicada na patogênese da endotoxemia equina. Endotoxinas foram capazes de aumentar a expressão de IL-8 nos neutrófilos in vitro (Neuder et al 2009) e no sangue quando injetadas sistemicamente (Nieto et al 2009). Além disso, o aumento da expressão de citocinas pro-inflamatórias (IL-1, IL-6, IL-8), no estágio de desenvolvimento da laminite, indica que a presença de quimiocinas atrativas de leucócitos (principalmente IL-8) pode desempenhar importante papel na migração leucocitária nos eventos iniciais da laminite (Belknap et al 2007, Faleiros et al 2009a, 2011b.…”

Section: Introductionunclassified

Avaliação clínica e hematológica de equinos submetidos ao modelo de laminite por oligofructose, tratados ou não com um agente antagonista de receptores CXCR1/2

et al. 2013

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Pesq. Vet. Bras. 33(8):992-998, agosto 2013 992 Avaliação clínica e hematológica de equinos submetidos ao modelo de laminite por oligofructose, tratados ou não com um agente antagonista de receptores CXCR1/2 Brazil. E-mail: faleirosufmg@gmail.com Leucocytes recruitment to tissues is an essential part of the innate immune response and an unregulated process can result in tissue damage. Thus, leucocytes infiltration has been implicated in the pathogenesis of acute laminitis. The objectives of this stud were to determine the effect of an antagonist for CXCR1/2, a chemokine receptor for neutrophils attraction on clinical signs and hematological parameters in horses given oligofructose to induce laminitis. Twelve horses were given oligofructose (10g/kg bw PO) in time 0 and divided into two groups: one treated (30mg/kg bw. ICXCR1/2 IV, times 6, 12, 18 e 24 h) and the other not treated. Cardiac and respiratory frequency, rectal temperature, mucous membrane colour, digital pulse, hoof sensitivity and Obel's grade of lameness were recorded. Values for RBC, WBC and blood glucose, BUN, creatinin, ALT, AST, alkaline phosphatase, GGT, total bilirubin and serum protein concentrations were measured on times 0, 6, 12, 18, 24, 36, 48, 60 e 72 h. All the horses given oligofructose developed signs of endotoxemia like diarrhea, fever and leukocytosis and laminitis. Also, CXCR1/2 antagonist treatment did not cause any adverse effects. However, this substance when injected intravenously (30mg/kg) 6/6 hours in 4 applications, did not ameliorate clinical and hematological signs of endotoxemia.

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Role of p38 MAPK in LPS induced pro-inflammatory cytokine and chemokine gene expression in equine leukocytes

Cited by 66 publications

References 49 publications

Induction of Endotoxin Tolerance by Pathogenic Neisseria Is Correlated with the Inflammatory Potential of Lipooligosaccharides and Regulated by MicroRNA-146a

Induction of Endotoxin Tolerance by Pathogenic Neisseria Is Correlated with the Inflammatory Potential of Lipooligosaccharides and Regulated by MicroRNA-146a

Induction and characterization of endotoxin tolerance in equine peripheral blood mononuclear cells in vitro

Avaliação clínica e hematológica de equinos submetidos ao modelo de laminite por oligofructose, tratados ou não com um agente antagonista de receptores CXCR1/2

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