scholarly journals Sex Differences in Peritraumatic Inflammatory Cytokines and Steroid Hormones Contribute to Prospective Risk for Nonremitting Posttraumatic Stress Disorder

2021 ◽  
Vol 5 ◽  
pp. 247054702110322
Author(s):  
Chloe S. Lalonde ◽  
Yara Mekawi ◽  
Kelly F. Ethun ◽  
Eleonore Beurel ◽  
Felicia Gould ◽  
...  
Keyword(s):  
Sex Differences ◽  
Inflammatory Cytokines ◽  
Lower Risk ◽  
Inflammatory Cytokine ◽  
Stress Disorder ◽  
Steroid Hormone ◽  
Trauma Exposure ◽  
Inflammatory Cytokine Response ◽  
Estradiol Levels ◽  
Pro Inflammatory Cytokines

Women are at higher risk for developing posttraumatic stress disorder (PTSD) compared to men, yet little is known about the biological contributors to this sex difference. One possible mechanism is differential immunological and neuroendocrine responses to traumatic stress exposure. In the current prospective study, we aimed to identify whether sex is indirectly associated with the probability of developing nonremitting PTSD through pro-inflammatory markers and whether steroid hormone concentrations influence this effect. Female ( n = 179) and male ( n = 197) trauma survivors were recruited from an emergency department and completed clinical assessment within 24 h and blood samples within ∼three hours of trauma exposure. Pro-inflammatory cytokines (IL-6, IL-1[Formula: see text], TNF, IFNγ), and steroid hormone (estradiol, testosterone, progesterone, cortisol) concentrations were quantified in plasma. Compared to men, women had a higher probability of developing nonremitting PTSD after trauma ( p = 0.04), had lower pro-inflammatory cytokines and testosterone ( p’ s<0.001), and had higher cortisol and progesterone ( p’ s<0.001) concentrations. Estradiol concentrations were not different between the sexes ( p = 0.24). Pro-inflammatory cytokines were a significant mediator in the relationship between sex and probability of developing nonremitting PTSD ( p < 0.05), such that men had higher concentrations of pro-inflammatory cytokines which were associated with lower risk of nonremitting PTSD development. This effect was significantly moderated by estradiol ( p < 0.05), as higher estradiol levels in men were associated with higher pro-inflammatory cytokine concentrations and lower risk for developing nonremitting PTSD. The current results suggest that sex differences in the pro-inflammatory cytokine response to trauma exposure partially mediate the probability of developing nonremitting PTSD, and that the protective ability to mount an pro-inflammatory cytokine response in men may depend on higher estradiol levels in the aftermath of trauma exposure.

Inhibition of Pro-Inflammatory Cytokine Secretion by Select Antioxidants in Human Coronary Artery Endothelial Cells

2020 ◽  
Vol 90 (1-2) ◽  
pp. 103-112 ◽  
Author(s):  
Michael J. Haas ◽  
Marilu Jurado-Flores ◽  
Ramadan Hammoud ◽  
Victoria Feng ◽  
Krista Gonzales ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Ascorbic Acid ◽  
Coronary Artery ◽  
Inflammatory Cytokines ◽  
Inflammatory Cytokine ◽  
Culture Media ◽  
Cytokine Secretion ◽  
Human Coronary Artery ◽  
Tnf Α ◽  
Pro Inflammatory Cytokines

Abstract. Inflammatory and oxidative stress in endothelial cells are implicated in the pathogenesis of premature atherosclerosis in diabetes. To determine whether high-dextrose concentrations induce the expression of pro-inflammatory cytokines, human coronary artery endothelial cells (HCAEC) were exposed to either 5.5 or 27.5 mM dextrose for 24-hours and interleukin-1β (IL-1β), interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor α (TNF α) levels were measured by enzyme immunoassays. To determine the effect of antioxidants on inflammatory cytokine secretion, cells were also treated with α-tocopherol, ascorbic acid, and the glutathione peroxidase mimetic ebselen. Only the concentration of IL-1β in culture media from cells exposed to 27.5 mM dextrose increased relative to cells maintained in 5.5 mM dextrose. Treatment with α-tocopherol (10, 100, and 1,000 μM) and ascorbic acid (15, 150, and 1,500 μM) at the same time that the dextrose was added reduced IL-1β, IL-6, and IL-8 levels in culture media from cells maintained at 5.5 mM dextrose but had no effect on IL-1β, IL-6, and IL-8 levels in cells exposed to 27.5 mM dextrose. However, ebselen treatment reduced IL-1β, IL-6, and IL-8 levels in cells maintained in either 5.5 or 27.5 mM dextrose. IL-2 and TNF α concentrations in culture media were below the limit of detection under all experimental conditions studied suggesting that these cells may not synthesize detectable quantities of these cytokines. These results suggest that dextrose at certain concentrations may increase IL-1β levels and that antioxidants have differential effects on suppressing the secretion of pro-inflammatory cytokines in HCAEC.

scholarly journals Distinct Effects of Escherichia coli,Pseudomonas aeruginosa and Staphylococcus aureus Cell Wall Component-Induced Inflammation on the Iron Metabolism of THP-1 Cells

2021 ◽  
Vol 22 (3) ◽  
pp. 1497
Author(s):  
Edina Pandur ◽  
Kitti Tamási ◽  
Ramóna Pap ◽  
Gergely Jánosa ◽  
Katalin Sipos
Keyword(s):  
Cell Wall ◽  
Inflammatory Cytokines ◽  
Iron Metabolism ◽  
Inflammatory Cytokine ◽  
Cytokine Production ◽  
Storage Proteins ◽  
Iron Storage ◽  
E Coli ◽  
Iron Storage Proteins ◽  
Pro Inflammatory Cytokines

Macrophages are essential immune cells of the innate immune system. They participate in the development and regulation of inflammation. Macrophages play a fundamental role in fighting against bacterial infections by phagocytosis of bacteria, and they also have a specific role in immunomodulation by secreting pro-inflammatory cytokines. In bacterial infection, macrophages decrease the serum iron concentration by removing iron from the blood, acting as one of the most important regulatory cells of iron homeostasis. We examined whether the Gram-positive and Gram-negative cell wall components from various bacterial strains affect the cytokine production and iron transport, storage and utilization of THP-1 monocytes in different ways. We found that S. aureus lipoteichoic acid (LTA) was less effective in activating pro-inflammatory cytokine expression that may related to its effect on fractalkine production. LTA-treated cells increased iron uptake through divalent metal transporter-1, but did not elevate the expression of cytosolic and mitochondrial iron storage proteins, suggesting that the cells maintained iron efflux via the ferroportin iron exporter. E. coli and P. aeruginosa lipopolysaccharides (LPSs) acted similarly on THP-1 cells, but the rates of the alterations of the examined proteins were different. E. coli LPS was more effective in increasing the pro-inflammatory cytokine production, meanwhile it caused less dramatic alterations in iron metabolism. P. aeruginosa LPS-treated cells produced a smaller amount of pro-inflammatory cytokines, but caused remarkable elevation of both cytosolic and mitochondrial iron storage proteins and intracellular iron content compared to E. coli LPS. These results prove that LPS molecules from different bacterial sources alter diverse molecular mechanisms in macrophages that prepossess the outcome of the bacterial infection.

scholarly journals P0527AROLE OF PROMOTING INFLAMMATION OF KLF6 IN ACUTE KIDNEY INURY

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Dan Li ◽  
Chenyu Li ◽  
Yan Xu
Keyword(s):  
Inflammatory Cytokines ◽  
Inflammatory Cytokine ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Tnf Α ◽  
Public Dataset ◽  
Anti Inflammatory ◽  
Anti Inflammatory Cytokine ◽  
Pro Inflammatory Cytokines

Abstract Background and Aims Acute kidney injury (AKI), commonly appeared in cardiac arrest, surgery and kidney transplantation which involved in ischemia-reperfusion (IR) injury of kidney. However, the mechanisms underlying inflammatory response in IR AKI is still unclear. Method Public dataset showed kruppel-like factor 6 (KLF6) was significantly highly expressed (P&lt;0.05) in AKI, implies KLF6 might be associated with AKI. To evaluate the mechanism of KLF6 on IR AKI, 30 rats were randomly divided into sham and IR group, and were sacrificed at 0 h, 3 h, 6 h, 12 h or 24 h after IR. Results The results showed KLF6 expression was peaking at 6 h after IR, and the expression of pro-inflammatory cytokines MCP-1 and TNF-α were increased both in serum and kidney tissues after IR, while anti-inflammatory cytokine IL-10 was decreased after IR. Furthermore, in vitro results showed KLF6 knock-down reduced the pro-inflammatory cytokines expression and increased the anti-inflammatory cytokines expression. Conclusion These results suggest that (1) KLF6 might be a novel biomarker for early diagnosis of AKI and (2) targeting KLF6 expression may offer novel strategies to protect kidneys from IR AKI Figure KLF6, AKI, Control Inflammation

scholarly journals Effect of Antimicrobial Agents on Inflammatory Cytokines in Acute Leptospirosis

2018 ◽  
Vol 62 (5) ◽  
Author(s):  
Narmada Fernando ◽  
Rajiva de Silva ◽  
Shiroma M. Handunnetti ◽  
Lilani Karunanayake ◽  
Nipun Lakshitha De Silva ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Proinflammatory Cytokines ◽  
Inflammatory Cytokine ◽  
Antimicrobial Agents ◽  
Interleukin 10 ◽  
Antimicrobial Treatment ◽  
Acute Stage ◽  
Cytokine Response ◽  
Inflammatory Cytokine Response

ABSTRACT The aim of this study was to assess the inflammatory cytokine response and possible association with antimicrobial treatment with penicillin, ceftriaxone, and doxycycline in acute leptospirosis. In the early acute stage, interleukin-10 (IL-10) levels were higher in mild cases than in severe cases ( P = 0.01). IL-6 and IL-8 levels were low in patients who received >5 antimicrobial doses ( P < 0.01). IL-8 levels were negatively correlated with the number of ceftriaxone doses administered ( r = −0.315; P = 0.031). Further studies are needed to evaluate the possible downregulation of proinflammatory cytokines by ceftriaxone in leptospirosis.

Abstract 205: Ouabain Activates the NF-κB Pathway in Macrophages via Na/K-ATPase/TLR4 Complex Leading to Pro-Inflammatory Cytokine Production

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Yiliang Chen ◽  
Roy L Silverstein
Keyword(s):  
Inflammatory Cytokines ◽  
Systemic Inflammation ◽  
Inflammatory Cytokine ◽  
Cytokine Production ◽  
Culture Media ◽  
Mrna Level ◽  
Mrna Levels ◽  
Inflammatory Cytokine Production ◽  
Protein Levels ◽  
Pro Inflammatory Cytokines

Cardiotonic steroids such as ouabain, digoxin, and marinobufagenin are known ligands for the plasma membrane receptor Na/K-ATPase (NKA). These ligands are able to stimulate interaction of the NKA with other membrane and cytosolic proteins leading to cellular events such as activation of kinase cascades and gene transcription. Endogenous cardiotonic steroids have been detected in human circulation and interestingly their levels were elevated in human patients with hypertension, congestive heart failure and diabetes, all of which were associated with chronic systemic inflammation. However, the role of cardiotonic steroids in systemic inflammation and immunity has not been well studied. We previously discovered that ouabain stimulated macrophages to produce pro-inflammatory cytokines, many of which are known targets of the transcription factor, NF-κB. Therefore, we hypothesized that ouabain activates NF-κB pathway leading to pro-inflammatory cytokine production in macrophages. Using Western blot and densitometry analysis, we showed that physiological concentrations of ouabain promoted IκBα degradation (as low as 5 nM ouabain decreased IκBα level by 66.8%±7.4%, n=4). This was accompanied by NF-κB translocation from cytoplasm to the nuclei as shown by immunocytochemistry (% of nuclei NF-κB signals increased from 30.5%±2.3% in control to 62.2%±2.6% in ouabain-treated macrophages, n>25). Moreover, via quantitative RT-PCR (n=3), we found that ouabain increased mRNA levels of pro-inflammatory cytokines such as MCP-1 (3.2±1.1 fold), TNF-α (59.7±35.6 fold), and CXCL-10 (2.8±1.6 fold), all of which are known NF-κB targets. Consistent with the increase in mRNA level, we found that MCP-1 protein levels were elevated in both cell lysates (1.8±0.3 fold) and culture media (1.4±0.1 fold; n=4). Addition of an NF-κB inhibitor blocked MCP-1 production induced by ouabain (n=4). Mechanistically, ouabain stimulated interaction between NKA and TLR4 as shown by Co-Immunoprecipitation (n=3). Blockade of TLR4 signaling using a specific peptide inhibitor, CLI-095, abolished the ouabain effect on NF-κB activation (n=3). We conclude that ouabain activates NF-κB through NKA/TLR4 complex leading to pro-inflammatory cytokine production by macrophages.

Pro-Inflammatory Cytokines Drive the Development of a Prothrombotic Platelet Phenotype in Inflammation and Aging

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3747-3747 ◽  
Author(s):  
Pavel Davizon-Castillo ◽  
Katrina Ashworth ◽  
Kelly Higa ◽  
Giovanny Hernandez ◽  
Sumitra Acharya ◽  
...  
Keyword(s):  
Platelet Activation ◽  
Inflammatory Cytokines ◽  
Platelet Function ◽  
Inflammatory Cytokine ◽  
Inflammatory Diseases ◽  
Hematopoietic Stem ◽  
Activation Profile ◽  
The Impact ◽  
Old Mice ◽  
Pro Inflammatory Cytokines

Abstract A high incidence of thrombotic events remains a potentially life-threatening consequence in a broad range of chronic inflammatory conditions including infection, obesity, cardiovascular disease (CVD), autoimmune disorders and aging. While deregulation of pro-coagulant molecules and activation of endothelial surfaces have been described as contributors to such thrombotic events, the extent to which the pro-inflammatory cytokine environment associated with inflammatory diseases may impact platelet reactivity, production and function remains to be further characterized. Hence, to directly interrogate the impact of inflammation on platelet function, we analyzed the platelet activation profile of washed platelets by flow cytometry using murine models of rheumatoid arthritis, collagen-induced arthritis (CIA) and of aging (24 month-old mice) to identify inflammation-induced changes in platelet function and production. Notably, both models revealed significant alterations to platelet function, characterized by increased exposure of P-selectin and the active form of the integrin aIIbb3 (JON/A) following platelet activation with thrombin. In addition, the exposure of phosphatidylserine (PS), measured with Lactadherin binding, was elevated in platelets from chronically inflamed CIA and old mice. As the pro-inflammatory cytokines interleukin-1 (IL-1) and tumor necrosis factor α (TNF) are key mediators of chronic inflammatory disease, we assessed using Tnf ΔARE transgenic mice, which overexpress TNF-α as well as young mice treated with daily injections of rIL1- for 20 days, whether chronic exposure these cytokines is sufficient to alter platelet function. Strikingly, despite increased peripheral blood platelet numbers, IL-1β treated mice did not exhibit a hyper-reactive platelet phenotype when compared to controls. On the other hand, platelets from Tnf ΔARE mice showed significant hyperactivity, and a single dose (24 hours) of murine rTNF or in vitro culture with rTNF also induced a robust platelet activation profile, suggesting that TNF acts directly on platelets and may play a more significant role than IL-1 in the development of an inflammation-driven prothrombotic platelet phenotype. Moreover, analysis of the hematopoietic stem cell (HSC) compartment in CIA and old mice revealed an increased frequency of previously-described CD41+ megakaryocyte-biased HSCs, which is recapitulated in mice chronically exposed to IL-1, suggesting that reprogramming of HSCs by pro-inflammatory cytokines likely fuels the overproduction of hyperactive platelets that contribute to thrombosis in chronic inflammatory diseases. Collectively, our findings suggest that IL-1 and TNFα contribute to inflammation-associated thrombosis via distinct mechanisms, with TNFα playing a particularly important role in platelet hyperactivation, and IL-1 impacting platelet production, likely in part via modulation of HSC fate. Hence, our findings identify a key role for distinct cytokine circuits in regulating platelet function, and implicate the pro-inflammatory cytokine environment as a key therapeutic target for modulation in patients at risk for inflammation-associated thrombotic events. Disclosures Di Paola: CSL BEhring: Consultancy; Biogen: Consultancy.

scholarly journals Altered overnight levels of pro-inflammatory cytokines in men and women with posttraumatic stress disorder

2019 ◽  
Vol 102 ◽  
pp. 114-120 ◽  
Author(s):  
Andreas Küffer ◽  
Laura D. Straus ◽  
Aric A. Prather ◽  
Sabra S. Inslicht ◽  
Anne Richards ◽  
...  
Keyword(s):  
Posttraumatic Stress Disorder ◽  
Posttraumatic Stress ◽  
Inflammatory Cytokines ◽  
Stress Disorder ◽  
Men And Women ◽  
Pro Inflammatory Cytokines

scholarly journals Propofol attenuates BV2 microglia inflammation via NMDA receptor inhibition

2018 ◽  
Vol 96 (3) ◽  
pp. 241-248 ◽  
Author(s):  
Qichao Wu ◽  
Yanjun Zhao ◽  
Xiangyuan Chen ◽  
Minmin Zhu ◽  
Changhong Miao
Keyword(s):  
Nmda Receptor ◽  
Inflammatory Cytokines ◽  
Inflammatory Cytokine ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Underlying Mechanism ◽  
Enzyme Expression ◽  
Bv2 Cells ◽  
Bv2 Microglia ◽  
Pro Inflammatory Cytokines

Activated microglia, involved in the occurrence and improvement of sepsis-associated encephalopathy, can induce the expression of pro-inflammatory cytokines and pro-inflammatory enzymes, resulting in inflammation-mediated neuronal cell death. It was reported that propofol could inhibit lipopolysaccharide (LPS) induced pro-inflammatory cytokine and pro-inflammatory enzyme expression in BV2 and primary microglial cells. However, the underlying mechanism is not well known. In the present study, we investigated whether and how propofol inhibited LPS-induced the expression of pro-inflammatory cytokines and pro-inflammatory enzymes in BV2 cells. LPS induced pro-inflammatory cytokine and pro-inflammatory enzyme expression, NF-κB, extracellular regulated kinase 1/2 (ERK), calcium (Ca2+)/calmodulin-dependent protein kinase II (CaMK II) phosphorylation, and BV2 cell Ca2+ accumulation. Propofol could reverse these effects induced by LPS. MK801, an inhibitor of the NMDA receptor, could attenuate LPS-induced Ca2+ accumulation, the expression of pro-inflammatory cytokines and pro-inflammatory enzymes, and phosphorylation of NF-κB, ERK, and CaMK II, which was similar to propofol. Moreover, these effects of propofol could be counteracted by rapastinel, an activator of the NMDA receptor. The present study suggested that propofol, via inhibiting the NMDA receptor, attenuating Ca2+ accumulation, and inhibiting CaMK II, ERK1/2, and NF-κB phosphorylation, down-regulated LPS-induced pro-inflammatory cytokine and pro-inflammatory enzyme expression.

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