Preliminary Evidence of Endotoxin Tolerance in Dairy Cows during the Transition Period

The blastogenic response of bovine peripheral blood mononuclear cells (PBMCs) to lipopolysaccharides (LPS) has been investigated for a long time in our laboratories. In particular, a possible correlation between the blastogenic response to LPS and the disease resistance of dairy cows has been suggested in previous studies. Isolated PBMCs from eight cows at three different time points during the transition period (T0 = 15 days before calving; T1 = 7 days post-calving; T2 = 21 days post-calving) were cultured in the presence or absence of LPS, and the blastogenic response was assayed 72 h after in vitro stimulation. Moreover, the gene expression of proinflammatory cytokines and kynurenine pathway molecules was investigated by real-time RT-PCR on both unstimulated and stimulated PBMCs. The cows were retrospectively divided into healthy and diseased, based on the development of peripartum diseases (subclinical ketosis and placenta retention). The comparison between healthy and diseased cows suggested that healthy animals seemed to better control the response to LPS. On the contrary, diseased animals showed a much higher inflammatory response to LPS. Moreover, cows were retrospectively classified as high and low responders based on the in vitro proliferative response of PBMCs to LPS, using the median value as a threshold. Unstimulated PBMCs of low responders showed higher expression of the proinflammatory cytokines Interleukin 1-β (IL-1β), Interleukin 6 (IL-6) and Tumor Necrosis Factor-α (TNF-α), compared to high responders. Our preliminary data suggest that, during the peripartum period, high responders seem to be more tolerant to endotoxins and develop a lower inflammatory response to different stressors. Instead, low responders could be more prone to the development of unwanted inflammatory conditions in response to mild/moderate stressors.

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Effect in vitro of a bacterial extract (OM-89) on interleukin 1 and interleukin 2 production by peripheral blood mononuclear cells from healthy subjects and rheumatoid arthritis patients

International Journal of Immunopharmacology ◽

10.1016/0192-0561(90)90011-b ◽

1990 ◽

Vol 12 (8) ◽

pp. 909-913 ◽

Cited By ~ 3

Author(s):

Jacques Clot ◽

Monique Andary

Keyword(s):

Rheumatoid Arthritis ◽

Peripheral Blood Mononuclear Cells ◽

Peripheral Blood ◽

Healthy Subjects ◽

Mononuclear Cells ◽

Interleukin 1 ◽

Interleukin 2 ◽

Peripheral Blood Mononuclear ◽

Blood Mononuclear Cells

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The effect of a leukodepletion model on the activation stage of platelets

Open Medicine ◽

10.2478/s11536-010-0062-1 ◽

2011 ◽

Vol 6 (2) ◽

pp. 181-184

Author(s):

Miodrag Vucic ◽

Ivan Tijanic ◽

Nenad Govedarevic ◽

Lana Macukanovic ◽

Zoran Pavlovic

Keyword(s):

Flow Cytometry ◽

Proinflammatory Cytokines ◽

Mononuclear Cells ◽

Buffy Coat ◽

The Other ◽

Therapeutic Doses ◽

Cell Counter ◽

Automatic Cell Counter

AbstractThe preparation of thrombocyte concentrates with filtration before storage (in-line) makes it possible to avoid the presence of mononuclear cells in the concentrate and proinflammatory cytokines. Therefore, this filtration may result with decreased activation of trombocyte receptors in vitro, which may improve therapeutic efficiancy. Methods. We compared two groups, each with 30 therapeutic doses of concentrated thrombocytes. We prepared the first group using the classic model from the buffy coat and the other with concentrated thrombocyte samples filtrated during sampling, so-called in-line, with the WBC filter Imuflex (Terumo). Mononuclear cells (MNC), thrombocyte, and erythrocyte counts in the units of concentrated thrombocytes were obtained on an automatic cell counter, and we used flow cytometry to measure the expression of surface thrombocyte receptors. The results demonstrated that the trombocytes prepared with pre-storage filtration contained a very low level of mononuclear cells and markedly reduced trombocyte receptors. Conclusion. The number of MNC and expression of surface thrombocyte receptors were markedly lower in the concentrated thrombocyte units prepared with in-line filtration. The thrombocytes prepared in this way contain fewer mononuclear cells, are of higher quality, are more functional, and may produce a better therapeutic effect in vivo.

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Chronic oral administration of P. gingivalis induces microglial activation and degeneration of dopaminergic neurons possibly through increase in gut permeability and peripheral IL-17A in LRRK2 R1441G mice

10.21203/rs.3.rs-34883/v1 ◽

2020 ◽

Author(s):

Yu-kun Feng ◽

Yan-Wen Peng ◽

Qiong-Li Wu ◽

Feng-Yin Liang ◽

Hua-Jing You ◽

...

Keyword(s):

Gut Microbiota ◽

Chronic Periodontitis ◽

Dopaminergic Neurons ◽

Microglial Activation ◽

Mononuclear Cells ◽

Late Onset ◽

Interleukin 1 ◽

Peripheral Inflammation ◽

Peripheral Blood Mononuclear

Abstract Background The R1441G mutation in the leucine-rich repeat kinase 2 (LRRK2) gene results in late-onset Parkinson’s disease (PD). Peripheral inflammation and gut microbiota are closely associated with the pathogenesis of PD. Chronic periodontitis is a common type of peripheral inflammation, which is associated with PD. Porphyromonas gingivalis (Pg), the most common bacterium causing chronic periodontitis, can cause alteration of gut microbiota. It is not known whether Pg-induced dysbiosis plays a role in the pathophysiology of PD. Methods In this study, live Pg were orally administrated to animals, three times a week for one month. Pg-derived lipopolysaccharide (LPS) was used to stimulate peripheral blood mononuclear cells in vitro. The effects of oral Pg administration on the gut and brain were evaluated through behaviors, morphology, and cytokine expression. Results Dopaminergic neurons in the substantia nigra were reduced and activated microglial cells were increased in R1441G mice given oral Pg. In addition, an increase in mRNA expression of tumor necrosis factor (TNF-α) and interleukin-1 β (IL-1β) as well as protein level of α-synuclein together with a decrease in zonula occludens-1 (Zo-1) were detected in the colon in Pg-treated R1441G mice. Furthermore, serum interleukin-17A (IL-17A) and brain IL-17 receptor A (IL-17RA) were increased in Pg-treated R1441G mice. Conclusions These findings suggest that LRRK2 causes gut leakage and further mediates peripheral IL-17A response in Pg-treated animals. We, thus, put forward the hypothesis that IL-17A in the serum may result in activation of the IL-17A-IL-17RA axis that aggravates dysfunction of dopaminergic neurons and provokes microglial activation in LRRK2 R1441G mice.

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In Vitro Investigation of the Roles of the Proinflammatory Cytokines Tumor Necrosis Factor-α and Interleukin-1 in Murine Osteoclastogenesis

Methods in Molecular Biology - The TNF Superfamily ◽

10.1007/978-1-4939-0669-7_10 ◽

2014 ◽

pp. 109-123 ◽

Cited By ~ 10

Author(s):

Joel Jules ◽

Xu Feng

Keyword(s):

Tumor Necrosis Factor ◽

Proinflammatory Cytokines ◽

Tumor Necrosis ◽

Tumor Necrosis Factor Α ◽

Interleukin 1 ◽

In Vitro Investigation ◽

Factor Α ◽

Necrosis Factor

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Inflammatory Response and Acute Phase Proteins in the Transition Period of High-Yielding Dairy Cows

Acute Phase Proteins as Early Non-Specific Biomarkers of Human and Veterinary Diseases ◽

10.5772/20747 ◽

2011 ◽

Cited By ~ 6

Author(s):

Erminio Trevisi ◽

Massimo Amadori ◽

Ivonne Archetti ◽

Nicola Lacetera ◽

Giuseppe Bertoni

Keyword(s):

Inflammatory Response ◽

Dairy Cows ◽

Acute Phase ◽

Transition Period ◽

Acute Phase Proteins

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Long noncoding RNA MALAT1 contributes to inflammatory response of microglia following spinal cord injury via the modulation of a miR-199b/IKKβ/NF-κB signaling pathway

AJP Cell Physiology ◽

10.1152/ajpcell.00278.2017 ◽

2018 ◽

Vol 315 (1) ◽

pp. C52-C61 ◽

Cited By ~ 37

Author(s):

Heng-Jun Zhou ◽

Li-Qing Wang ◽

Duan-Bu Wang ◽

Jian-Bo Yu ◽

Yu Zhu ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Inflammatory Response ◽

Signaling Pathway ◽

Proinflammatory Cytokines ◽

Long Noncoding Rna ◽

Noncoding Rna ◽

Tnf Α ◽

Cord Injury

Long noncoding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) was widely recognized to be implicated in human cancer, vascular diseases, and neurological disorders. This study was to explore the role and underlying mechanism of MALAT1 in acute spinal cord injury (ASCI). ASCI models in adult rats were established and demonstrated by a numerical decrease in BBB scores. Expression profile of MALAT1 and miR-199b following ASCI in rats and in vitro was determined using quantitative real-time PCR. RNA pull-down assays combined with RIP assays were performed to explore the interaction between MALAT1 and miR-199b. In the present study, MALAT1 expression was significantly increased (2.4-fold that of control) in the spinal cord of the rat contusion epicenter accompanied by activation of IKKβ/NF-κB signaling pathway and an increase in the level of proinflammatory cytokines TNF-α and IL-1β. Upon treatment with LPS, MALAT1 expression dramatically increased in the microglia in vitro, but knockdown of MALAT1 attenuated LPS-induced activation of MGs and TNF-α and IL-1β production. Next, we confirmed that LPS-induced MALAT1 activated IKKβ/NF-κB signaling pathway and promoted the production of proinflammatory cytokines TNF-α and IL-1β through downregulating miR-199b. More importantly, MALAT1 knockdown gradually improved the hindlimb locomotor activity of ASCI rats as well as inhibited TNF-α, IL-1β levels, and Iba-1 protein, the marker of activated microglia in injured spinal cords. Our study demonstrated that MALAT1 was dysregulated in ASCI rats and in LPS-activated MGs, and MALAT1 knockdown was expected to attenuate ASCI through repressing inflammatory response of MGs.

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Multiple sclerosis: myelin basic protein induced mRNA expression of proinflammatory cytokines in mononuclear cells is suppressed by interferon-β 1b in vitro

European Journal of Neurology ◽

10.1111/j.1468-1331.1997.tb00385.x ◽

1997 ◽

Vol 4 (5) ◽

pp. 460-467 ◽

Cited By ~ 4

Author(s):

P. Kivisäkk ◽

W. Tian ◽

S. Fredrikson ◽

H. Link ◽

M. Söderström

Keyword(s):

Multiple Sclerosis ◽

Myelin Basic Protein ◽

Mrna Expression ◽

Proinflammatory Cytokines ◽

Mononuclear Cells ◽

Basic Protein ◽

Interferon Β

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In Vitro Exploratory Studies of Haptoglobin Polymorphisms and Their Effect on Cytokine Release from Cultured Mononuclear Cells in Sickle Cell Disease.

Blood ◽

10.1182/blood.v112.11.1441.1441 ◽

2008 ◽

Vol 112 (11) ◽

pp. 1441-1441

Author(s):

Komal Bora ◽

Kavita Natarajan ◽

Ferdane Kutlar ◽

Hanfang Zhang ◽

Hongyan Xu ◽

...

Keyword(s):

Inflammatory Response ◽

Mononuclear Cells ◽

Susceptibility Gene ◽

Vascular Complications ◽

Diabetic Patients ◽

Cytokine Release ◽

Significant Difference ◽

Hb S ◽

Multiplex Bead

Abstract The deleterious effects of hemolysis through its end product cell free hemoglobin(Hb) as a nitric oxide (NO) scavenger is well established and has been incriminated in the pathogenesis of some complications of SCD such as pulmonary hypertension, leg ulcers, renal dysfunction, and possibly stroke. These observations have led some investigators to hypothesize that these complications form a subphenotype of SCD related predominantly to hemolysis and endothelial dysfunction. In hemolytic states Hb released from RBC complexes with Haptoglobin (Hp) and is removed from the circulation by macrophages and monocytes through binding CD163, the Hb scavenger receptor expressed on these cells. When the binding capacity of Hp is exceeded, the concentration of free Hb rises in the plasma. Hp is a polymorphic protein encoded by a gene on chromosome 16q2.2; there are two allelic variants, Hp 1 and Hp 2. Hp 2 is believed to have resulted from an intragenic duplication event, leading to an elongated Hp a-chain. Individuals homozygous for the long a2 chain express large multimeric molecules (Hp 2-2). During the past decade, a considerable body of evidence has accumulated suggesting that Hp-2 allele is a major susceptibility gene for the development of vascular complications (coronary artery restenosis and development of cardiovascular disease) especially in diabetic patients. It has been hypothesized that the Hb-Hp2 complexes have a 10-fold greater affinity for the CD 163 receptor, and the binding of Hb-Hp2 complexes generates a more powerful inflammatory response with a more prominent cytokine release. Recently, we performed a preliminary analysis of the distribution of Hp1 and Hp2 alleles among pediatric and adult SCD patients and reported a significantly higher allele frequency for Hp2 among pediatric patients, suggesting a survival advantage for carriers of Hp1 allele (Yaun et al, Blood, 2005). We now report the results of an exploratory in vitro study of cytokine release from purified mononuclear cells obtained from a normal control and an SCD patient following exposure to Hb-Hp1-1 and Hb-Hp2-2 complexes. Mononuclear cells (106/well) isolated by Ficoll-Hypaque density gradient were incubated with Hb A-Hp1-1, Hb A-Hp2-2, Hb S Hp1-1, and Hb S-Hp2-2 complexes with a 1:1 ratio (wt/wt) at a final concentration of 1 mg/ml. After 24 hr incubation at 37°C, the supernatants collected after centrifugation were used for cytokine assays by a multiplex bead method. A blank (medium only), Hb A and Hb S without Hp were also incubated with mononuclear cells. Multiplex bead assays showed that cytokine release (GM-CSF, IL-1b, IL-6, IL-10, and TNFa) was much higher (3–12 fold) from both the control and SCD mononuclear cells upon exposure to Hb-Hp2-2 complexes, but much less or no effect by Hb-Hp1-1. The fold induction of TNFa and IL-1b was much higher in SCD cells than in control cells. There was no significant difference between Hb A and Hb S in terms of cytokine release when they were complexed with either Hp1-1 or Hp2-2, suggesting that the cytokine release was predominantly related to Hp type but not to Hb. Pure Hb A and Hb S increased cytokines over the control (blank) but to a significantly smaller extent than Hb (A or S) Hp-2-2 complexes. These preliminary results are confirmatory of a deleterious effect of the Hp2-2 genotype through a more pronounced inflammatory response and are suggestive of a potential novel mechanism whereby hemolysis could result in adverse outcomes related to Hp polymorphisms. If confirmed in larger studies and through phenotypic associations, attenuation of this response via anti-inflammatory modalities may provide a therapeutic strategy. Figure Figure

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