scholarly journals MAPKs ERK and p38, but not JNK Phosphorylation, Modulate IL-6 and TNF-α Secretion Following OK-432 In Vitro Stimulation of Purified Human Monocytes

2011 ◽  
Vol 74 (2) ◽  
pp. 114-125 ◽  
Author(s):  
C. Olsnes ◽  
J. Olofsson ◽  
H. J. Aarstad
Keyword(s):  
Human Monocytes ◽  
Tnf Α ◽  
Stimulation Of

scholarly journals Ureaplasma urealyticum Modulates Endotoxin-Induced Cytokine Release by Human Monocytes Derived from Preterm and Term Newborns and Adults

2001 ◽  
Vol 69 (6) ◽  
pp. 3906-3915 ◽  
Author(s):  
Winston M. Manimtim ◽  
Jeffrey D. Hasday ◽  
Lisa Hester ◽  
Karen D. Fairchild ◽  
Judith C. Lovchik ◽  
...  
Keyword(s):  
Proinflammatory Cytokines ◽  
Ureaplasma Urealyticum ◽  
Human Monocytes ◽  
Cytokine Release ◽  
Proinflammatory Response ◽  
Pediatr Infect ◽  
High Inoculum ◽  
Tnf Α ◽  
Adult Cells

ABSTRACT We previously observed that Ureaplasma urealyticumrespiratory tract colonization in infants with a birth weight of ≤1,250 g was associated with increases in the tracheal aspirate proinflammatory cytokines tumor necrosis factor alpha (TNF-α) and interleukin-8 (IL-8) relative to the counterregulatory cytokine IL-6 during the first week of life (A. M. Patterson, V. Taciak, J. Lovchik, R. E. Fox, A. B. Campbell, and R. M. Viscardi, Pediatr. Infect. Dis. J. 17:321–328, 1998). We hypothesized thatU. urealyticum alters the host immune response in the presence of a coinflammatory stimulus (e.g., bacterial infection or hyperoxia) by shifting the balance of cytokine expression towards the proinflammatory cytokines. To test this hypothesis, we compared the release of TNF-α, IL-8, IL-6, and IL-10 in vitro by unstimulated andU. urealyticum (with or without lipopolysaccharide [LPS])-stimulated human monocytes from adult peripheral blood and from term and preterm cord blood. U. urealyticum alone and in combination with LPS induced concentration- and development-dependent changes in cytokine release. In vitro inoculation with low-inoculum U. urealyticum (103color-changing units [CCU]) (i) partially blocked the LPS-stimulated IL-6 release by all cells and reduced LPS-stimulated IL-10 release by preterm cells, (ii) stimulated TNF-α and IL-8 release by preterm cells, and (iii) augmented LPS-stimulated TNF-α release in all cells. In preterm cells, high-inoculum U. urealyticum(106 CCU) (i) stimulated TNF-α and IL-8, but not IL-6 or IL-10, release and (ii) augmented LPS-stimulated TNF-α and IL-8 release. High-inoculum U. urealyticum (i) stimulated release of all four cytokines in term cells and IL-8 release in adult cells and (ii) augmented LPS-induced TNF-α, IL-10, and IL-8 release in term cells but did not significantly affect LPS-induced cytokine release in adult cells. We speculate that U. urealyticum enhances the proinflammatory response to a second infection by blocking expression of counterregulatory cytokines (IL-6 and IL-10), predisposing the preterm infant to prolonged and dysregulated inflammation, lung injury, and impaired clearance of secondary infections.

In-vitro stimulation of TNF-α from human whole blood by cell-free supernatants of Gram-positive bacteria

Cytokine ◽  
1992 ◽  
Vol 4 (5) ◽  
pp. 397-402 ◽  
Author(s):  
Katherine Bayston ◽  
Mark Tomlinson ◽  
Jonathan Cohen
Keyword(s):  
Whole Blood ◽  
Gram Positive ◽  
Human Whole Blood ◽  
Gram Positive Bacteria ◽  
Tnf Α ◽  
Stimulation Of

scholarly journals Endothelin-1 stimulates human monocytes in vitro to release TNF-α , IL-1β and IL-6

1993 ◽  
Vol 2 (6) ◽  
pp. 417-422 ◽  
Author(s):  
E. Helset ◽  
T. Sildnes ◽  
R. Seljelid ◽  
Z.S. Konopski
Keyword(s):  
Human Monocytes ◽  
Endothelin 1 ◽  
Tnf Α

scholarly journals Modulation of Endotoxin- and Enterotoxin-Induced Cytokine Release by In Vivo Treatment with β-(1,6)-Branched β-(1,3)-Glucan

1999 ◽  
Vol 67 (1) ◽  
pp. 244-252 ◽  
Author(s):  
Jindrich Soltys ◽  
Mark T. Quinn
Keyword(s):  
Proinflammatory Cytokines ◽  
Necrosis Factor Alpha ◽  
Enhanced Production ◽  
Tnf Α ◽  
Host Mortality ◽  
Toxic Shock Syndrome Toxin ◽  
Stimulation Of ◽  
In Cells

ABSTRACT Leukocytes activated by endotoxin or enterotoxins release proinflammatory cytokines, thereby contributing to the cascade of events leading to septic shock. In the present studies, we analyzed the effects of in vivo administration of a soluble immunomodulator, β-(1,6)-branched β-(1,3)-glucan (soluble β-glucan), on toxin-stimulated cytokine production in monocytes and lymphocytes isolated from treated mice. In vitro stimulation of lymphocytes isolated from soluble β-glucan-treated mice with lipopolysaccharide (LPS) resulted in enhanced production of interleukin-6 (IL-6) and suppressed production of tumor necrosis factor alpha (TNF-α), while stimulation of these cells with staphylococcal enterotoxin B (SEB) or toxic shock syndrome toxin 1 (TSST-1) resulted in enhanced production of gamma interferon (IFN-γ) and suppressed production of IL-2 and TNF-α compared to that in cells isolated from untreated mice. In vitro stimulation of monocytes isolated from soluble β-glucan-treated mice with LPS also resulted in suppressed TNF-α production, while stimulation of these cells with SEB or TSST-1 resulted in suppressed IL-6 and TNF-α production compared to that in cells isolated from untreated mice. Thus, the overall cytokine pattern of leukocytes from soluble β-glucan-treated mice reflects suppressed production of proinflammatory cytokines, especially TNF-α. Taken together, our results suggest that treatment with soluble β-glucan can modulate the induction cytokines during sepsis, resulting in an overall decrease in host mortality.

scholarly journals The IgG Fc receptor, CD16, interacts with LPS and is internalized during the in vitro stimulation of human monocytes.

2015 ◽  
Vol 6 ◽  
Author(s):  
Paniagua Natsuko ◽  
García Cesar ◽  
Salgado Alfonso ◽  
Ventura-Ayala Laura ◽  
Navarro María Del Carmen ◽  
...  
Keyword(s):  
Fc Receptor ◽  
Human Monocytes ◽  
Stimulation Of

scholarly journals Modulation of TNF-α Secretion in Peripheral Blood Mononuclear Cells by Cocoa Flavanols and Procyanidins

2002 ◽  
Vol 9 (3) ◽  
pp. 135-141 ◽  
Author(s):  
T. K. Mao ◽  
J. van de Water ◽  
C. L. Keen ◽  
H. H. Schmitz ◽  
M. E. Gershwin
Keyword(s):  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Resting Cells ◽  
Peripheral Blood Mononuclear ◽  
Tnf Α ◽  
Blood Mononuclear Cells ◽  
Stimulation Of

Epidemiological reports have suggested that the consumption of foods rich in flavonoids is associated with a lower incidence of certain degenerative diseases, including cardiovascular disease. Flavanols and their related oligomers, the procyanidins CFP, isolated from cocoa can modulate the production and level of several signaling molecules associated with immune function and inflammationin vitro, including several cytokines and eicosanoids. To further elucidate the potential immuno-modulatory functions of flavanol-rich cocoa, the present investigation examined whether isolated CFP fractions (monomers through decamers) influence the secretion of tumor necrosis factor-α (TNF-α) from resting and phytohemagluttinin (PHA)-stimulated human peripheral blood mononuclear cells (PBMC). We used anin vitroculture system where PBMC from 14 healthy subjects were introduced to individual CFP fractions for 72 h prior to measuring the levels of TNF-α released. The intermediate-sized CFP fractions (tetramers through octamers) were the most active on resting cells, causing a 3–4 fold increase in TNF-α relative to media baseline. The monomers and dimers were the least stimulatory of the fractions tested, displaying a 42 and 31% increase, respectively, over media control, whereas the trimers, nonamers and decamers showed an intermediate stimulation of this cytokine. In the presence of PHA, the intermediate-sized CFP fractions again were the most active, enhancing TNF-α secretion in the range of 48–128% relative to the PHA control. The monomers and dimers were slightly inhibitory (–1.5 and –15%, respectively), while trimers, nonamers and decamers stimulated moderate increases in TNF-α levels (13, 19 and 15%, respectively). The above results lend support to the concept that CFP can be immunomodulatory. The stimulation of TNF-α secretion may contribute to the putative beneficial effects of dietary flavanoids against microbial infection and tumorigenesis.

scholarly journals CD4 T-cell immune stimulation of HER2 + breast cancer cells alters response to trastuzumab in vitro

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Patrick N. Song ◽  
Ameer Mansur ◽  
Kari J. Dugger ◽  
Tessa R. Davis ◽  
Grant Howard ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
T Cell ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Immune Stimulation ◽  
Her2 Breast Cancer ◽  
Tnf Α ◽  
Stimulation Of

Abstract Introduction The HER2 + tumor immune microenvironment is composed of macrophages, natural killer cells, and tumor infiltrating lymphocytes, which produce pro-inflammatory cytokines. Determining the effect of T-cells on HER2 + cancer cells during therapy could guide immunogenic therapies that trigger antibody-dependent cellular cytotoxicity. This study utilized longitudinal in vitro time-resolved microscopy to measure T-cell influence on trastuzumab in HER2 + breast cancer. Methods Fluorescently-labeled breast cancer cells (BT474, SKBR3, MDA-MB-453, and MDA-MB-231) were co-cultured with CD4 + T-cells (Jurkat cell line) and longitudinally imaged to quantify cancer cell viability when treated with or without trastuzumab (10, 25, 50 and 100 μg/mL). The presence and timing of T-cell co-culturing was manipulated to determine immune stimulation of trastuzumab-treated HER2 + breast cancer. HER2 and TNF-α expression were evaluated with western blot and ELISA, respectively. Significance was calculated using a two-tailed parametric t-test. Results The viability of HER2 + cancer cells significantly decreased when exposed to 25 μg/mL trastuzumab and T-cells, compared to cancer cells exposed to trastuzumab without T-cells (p = 0.01). The presence of T-cells significantly increased TNF-α expression in trastuzumab-treated cancer cells (p = 0.02). Conversely, cancer cells treated with TNF-α and trastuzumab had a similar decrease in viability as trastuzumab-treated cancer cells co-cultured with T-cells (p = 0.32). Conclusions The presence of T-cells significantly increases the efficacy of targeted therapies and suggests trastuzumab may trigger immune mediated cytotoxicity. Increased TNF-α receptor expression suggest cytokines may interact with trastuzumab to create a state of enhanced response to therapy in HER2 + breast cancer, which has potential to reducing tumor burden.

Ivig Negatively Regulates LPS-Induced Monocytes Activation Through a Microrna-146a Related Mechanism

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3274-3274
Author(s):  
Lionel Loubaki ◽  
Renée Bazin
Keyword(s):  
Immune Response ◽  
Inflammatory Cytokines ◽  
Small Rna ◽  
Cytokine Production ◽  
Innate Immune ◽  
Human Monocytes ◽  
Monocytic Cells ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Stimulation Of

Abstract Abstract 3274 Background: Cells from the monocytic lineage are known to play a central role in the immune defense against pathogens. In the adaptive immune response, they act as antigen presenting cells to trigger T and B cell responses. Monocytic cells also participate in innate immunity following recognition of pathogen-associated molecular patterns (PAMPs) such as bacterial lipopolysaccharides (LPS), which leads to their activation and release of very potent inflammatory mediators. The innate immune response thus needs to be tightly regulated to control not only its onset, but also its termination in order to avoid excessive inflammation. Recent studies have shown that the differentiation and functions of monocytic cells involve small RNA species, named microRNAs (miRNAs). MiRNAs are 21–23 nucleotide long single strand RNAs, which mainly cause gene silencing by degradation of target mRNAs or by inhibition of translation. Among them, miR-146a has captivated interest as it plays an important role in the negative regulation of acute inflammatory responses during activation of the innate immune system. In fact, it has been shown that miR-146a expression is gradually increased in THP-1 monocytic cells following stimulation with LPS or cytokines (e.g. IL-1β and TNF-α) via a NF-κB dependent pathway. MiR-146a inhibits the expression of IRAK1 and TRAF6 leading to the subsequent suppression of NF-κB activity. Consequently, the expression of NF-κB target genes such as IL-1β, TNF-α and PU.1 is suppressed. Therefore, miR146a controls NF-κB signaling via a negative feedback regulation loop and thus can be considered as an anti-inflammatory mediator. IVIg is a therapeutic preparation of polyclonal human IgG isolated from the plasma of thousands of healthy donors. IVIg is well known for its anti-inflammatory effects on a variety of immune cells and processes. More precisely, it has been shown to abrogate the capacity of monocyte-derived dendritic cells to secrete pro-inflammatory cytokines while increasing the expression of anti-inflammatory cytokines such as IL-10. We thus hypothesize that at least some of the anti-inflammatory effects of IVIg on monocytic cells could be triggered through the modulation of miR-146a expression. Objectives: To evaluate the involvement of miR-146a in the anti-inflammatory effects of IVIg following LPS stimulation of human monocytes. Methods: Human monocytes were obtained from the blood of healthy volunteers and treated with LPS (1 mg/mL) or IVIg (15 mg/mL) alone or alternatively, pretreated with LPS followed by addition of IVIg. Pre-treatment with LPS was done during for 4 h prior to addition of IVIg for 3, 6, 12 and 24 hours. Cells were then recovered and separated in two parts. The first part was used to extract the small RNA fraction of total RNA for miRNA analysis and the second part was used for protein isolation. The miR-146a level was measured by real time PCR while NF-kB and IRF4 protein levels were evaluated by western blotting. Finally, the expression of the transcription factor PU.1 was evaluated by flow cytometry. Results: Our preliminary data revealed that addition of IVIg to LPS-pretreated human monocytes resulted in a significant upregulation of miR-146a expression associated with a significant reduction in NF-κB expression. Furthermore, the expression of the PU.1/IRF4 transcriptional activator complex involved in the stimulation of inflammatory cytokine production was modulated. Indeed, we found that the expression PU.1 was reduced in IVIg-treated cells whereas IRF4 expression was increased, thus promoting the IRF4-mediated cytokine production inhibitory pathway. Conclusion: Our preliminary data suggest that in human monocytes, the anti-inflammatory effects of IVIg may involve miR-146a negative feedback loop regulation of NF-κB activity. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Soluble ST2 Does Not Regulate TNF-α and IL-6 Production in Dengue Virus-Infected Human Monocytes

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Marisol Pérez-Acosta ◽  
Félix Giovanni Delgado ◽  
Jaime E. Castellanos
Keyword(s):  
Dengue Virus ◽  
Viral Antigen ◽  
Mononuclear Cells ◽  
Acute Infection ◽  
Denv Infection ◽  
Human Monocytes ◽  
Peripheral Blood Mononuclear ◽  
Soluble St2 ◽  
Tnf Α

Dengue virus (DENV) produces an acute infection that results in the overproduction of proinflammatory cytokines. Although increased levels of the immunoregulator soluble ST2 (sST2) protein have been reported in the serum of patients with dengue, its importance during DENV infection remains unclear. The purpose of this study was to evaluate the effect of a recombinant human sST2 protein on the production of TNF-α and IL-6 in an in vitro model of DENV infection. Peripheral blood mononuclear cells (PBMCs) were permissive to in vitro DENV infection since viral antigen was detected in CD14+ monocytes by flow cytometry (median, 1%; range, 0–2.2), and in their supernatants TNF-α and IL-6 were detected. However, sST2 protein was not detected. Using multiple staining on infected PBMC we found that only CD14+ cells produced TNF-α and IL-6. Treatment with human recombinant sST2 protein decreased lipopolysaccharide-induced monocyte TNF-α and IL-6 production. However, this effect was not observed when the monocytes were pretreated with sST2 and later infected with DENV-2. These results suggest that sST2 has different roles in the regulation of TNF-α and IL-6 expression in human monocytes stimulated with LPS and DENV-2.

Sign in / Sign up

Export Citation Format

Share Document