scholarly journals Secretion of proinflammatory cytokines by normal human melanocytes in response to lipopolysaccharide.

2011 ◽  
Vol 58 (4) ◽  
Author(s):  
Irena Tam ◽  
Krystyna Stępień
Keyword(s):  
Immune System ◽  
Inflammatory Cytokines ◽  
Proinflammatory Cytokines ◽  
Large Body ◽  
Dependent Manner ◽  
Skin Immune System ◽  
Human Melanocytes ◽  
Tnf Α ◽  
Normal Human ◽  
Dose Dependent

A large body of evidence suggests that epidermal melanocytes are an integral part of the skin immune system and can be considered immunocompetent cells. Recently, it has been reported that human melanocytes constitutively express Toll-like receptors and may be involved in the induction of several inflammatory cytokines. In the study the secretion of IL-1β, IL-6 and TNF-α by cultured normal melanocytes was investigated after stimulation with lipopolysaccharide. LPS increased the secretion of IL-1β in a dose-dependent manner. IL-1β stimulated release of IL-6 and TNF-α by melanocytes, whereas LPS activated production of TNF-α, but not of IL-6. These observations indicate that LPS can participate in the regulation of cytokine activity in normal human melanocytes and suggest that cytokines released by melanocytes could affect melanocytes themselves or/and other cells of the epidermis.

scholarly journals Plasma levels of melatonin, certain cytokines and placental growth factor at non-pharmacological correction of pineal function in pregnant women with intrauterine growth restriction

2020 ◽  
Vol 8 (2) ◽  
Author(s):  
A. Berbets ◽  
Keyword(s):  
Immune System ◽  
Growth Factor ◽  
Pineal Gland ◽  
Pregnant Women ◽  
Inflammatory Cytokines ◽  
Proinflammatory Cytokines ◽  
Placental Growth Factor ◽  
Placental Insufficiency ◽  
Tnf Α ◽  
Anti Inflammatory

The pineal gland produces the important hormone melatonin, the level of which in the blood of pregnant women decreases in case of placental insufficiency. The effect of dysfunction of the pineal gland on the immune system of pregnant women and on the angiogenic activity of the placenta during pregnancy remains insufficiently studied. Objective: to establish the effect of our method of non-drug correction of function of pineal gland on the state of the cytokine part of the immune system and on the synthesis of placental growth factor (PlGF) in pregnant women with placental insufficiency manifesting as fetal intrauterine growth restriction (IUGR). Material and methods. 46 pregnant women with IUGR at 30-36 weeks of gestation were examined. The group was divided into two subgroups: with non-drug correction of the pineal gland function (n = 25) and without correction (n = 21). The method of correction included a set of measures of following of lighting regimen, activity and sleep for 14 days. The control group consisted of 20 women with uncomplicated pregnancy. Levels of melatonin, PlGF, TNF-α, IL-1β, IL-6, IL-4, IL-10 were determined in the venous blood by enzyme-linked immunosorbent assay. Results. It was established that the concentration of melatonin in the blood of pregnant women with IUGR was significantly reduced, as well as the concentration of PlGF (p < 0.01). Significant changes were also found in pregnant women with placental insufficiency, namely, increased concentrations of proinflammatory cytokines, such as TNF-α (p < 0.05), IL-1-β (p < 0.001) and IL-6 (p < 0.05), comparing to healthy pregnant women. Also, in the group of pregnant women with IUGR the levels of anti-inflammatory cytokines IL-4 (p <0.001) and IL-10 (p < 0.001) were elevated in comparison to the control group. After application of the developed complex of non-drug correction of pineal gland function, the concentration of melatonin in the blood of pregnant women in the subgroup of correction increased significantly, comparing to the subgroup without correction (p < 0.001), as well as the level of PlGF (p < 0.05). Also, significantly lower levels of proinflammatory cytokines TNF-α, IL-1-β and IL-6 were observed in pregnant women in the subgroup of correction (p < 0.01). Regarding anti-inflammatory cytokines, under the influence of the developed complex of measures there was a decrease in the level of IL-4 and an increase in the level of IL-10 (p < 0.01). Conclusions. When the measures, aimed at non-drug correction of function of pineal gland, are applied in pregnant women with placental insufficiency, manifested as IUGR, the following changes are observed: increased of plasma levels of melatonin and placental growth factor, decreased of levels of proinflammatory cytokines. We suggest that the pineal gland exerts its effect on the immune system through melatonin, which moderates the activity of pro- and anti-inflammatory cytokines, thereby reducing the influence of inflammation on placental tissue, what results in increasing of concentrations of placental growth factor in the blood of pregnant women.

scholarly journals Anti-inflammatory Effect of the Peptide LKEKK

2021 ◽  
Vol 6 (5) ◽  
Keyword(s):  
High Specificity ◽  
Dependent Manner ◽  
Thymosin Α1 ◽  
Tnf Α ◽  
Normal Human ◽  
Anti Inflammatory ◽  
Interferon Α2 ◽  
Dose Dependent

We have established that the peptide LKEKK (Np5) corresponding to the sequence 16-20 of thymosin-α1 and to the sequence 131-135 of interferon-α2, in the concentration range 50 300 µg/ear reduces in a dose-dependent manner phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced skin edema in mice .Tested in parallel peptide with inverted sequence (iNp5, KKEKL, 150-300 µg/ear) was inactive, indicating high specificity of the Np5 action. In the concentration range of 5 20 µM Np5 significantly decrease the TNF-α-induced production by normal human keranocytes of pro-inflammatory mediators IL-6 and IL-1β. Thus, Np5t has a pronounced anti-inflammatory activity in vivo and in vitro.

Anti-Inflammatory Effects of Moxifloxacin with and without Anti Toll-Like Receptors and Protein-Tyrosine-Kinase Inhibitors in Human Monocytes Stimulated with Aspergillus fumigatus.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4217-4217
Author(s):  
Ina Fabian ◽  
Avital Levitov ◽  
Debby Haite ◽  
Drora Halperin ◽  
Jacob Romano ◽  
...  
Keyword(s):  
Invasive Aspergillosis ◽  
Aspergillus Fumigatus ◽  
Proinflammatory Cytokines ◽  
Autologous Serum ◽  
Dependent Manner ◽  
Protein Tyrosine ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Dose Dependent ◽  
Cytokines Secretion

Abstract Invasive aspergillosis is a life-threatening disease in immunocompromised patients. Studies have shown that conidia from Aspergillus fumigatus (AF) induce the release of proinflammatory cytokines from leukocytes and provoke an inflammatory response. Although cytokines such as TNF-α and IL-8 are critical for optimal host defenses, in some patients with invasive aspergillosis such as patients with neutropenia or allergic bronchopulmonary aspergillosis, limiting the immune response by decreasing cytokine release could prove beneficial. We have shown that the fluoroquinolone moxifloxacin (MXF) conferred protective anti-inflammatory effects in a murine model of Candida pneumonia in immune suppressed animals (AAC46: 2442, 2002). In the present study, we investigated the effect of MXF on cytokine response and signal transduction mechanisms in human peripheral blood monocytes (PBMN) of healthy individuals stimulated with conidia of AF. PBMN incubated with 2% autologous serum were stimulated for 6 h with AF (1.5x106/ml) and cytokine secretion was measured with and without the addition of MXF. Secretion of IL-8, IL-1β and TNF-α was significantly enhanced by AF (4.3, 8.2 and 7-fold respectively), while MXF (5–20μg/ml) inhibited the cytokines secretion in a dose dependent manner up to 46%, 72% and 73% respectively (p&lt;0.05). Recognition of invading microorganisms by the innate immune system is a first step in their successful elimination. In the mouse, toll-like receptor (TLR) 2 and 4 were found to be essential for AF-induced activation of macrophages while conflicting data have been published regarding human macrophages. We treated PBMN with blocking antibodies (Ab) directed against TLR2 and TLR4 and found that both TLRs are involved in cellular sensing of AF. Blocking of PBMN with a combination of anti-TLR2 and 4 Ab before exposure to AF resulted in 42%, 46% and 61% decrease in IL-8, IL-1β and TNF-α, secretion, respectively. Pre-incubation of the cells with MXF (20 μg/ml) and the combined anti-TLR2 and 4 Ab resulted in an additional decrease in the cytokines secretion up to 60%, 68% and 80%, respectively. Previous studies have implicated activation of protein tyrosine kinases (PTK) in LPS-induced NFkB activation and TNF-α production. In-vitro studies performed previously by us showed that MXF inhibits NFkB and MAPK activation and the synthesis of proinflammatory cytokines in activated human monocytic cells (AAC48:1974, 2004). In the present study we stimulated PBMN with AF, with and without the PTK inhibitor, genistein (Gen) in the presence and absence of MXF. Gen (5–40 μM) inhibited in a dose dependent manner IL-8 secretion up to 25%. Pre-incubation of PBMN with MXF (20 μg/ml) and Gen resulted in an additional decrease in IL-8 secretion up to 49%. Our results indicate that the anti-inflammatory effect of MXF in AF-stimulated PBMN does not signal via TLR2 or TLR4, nor via PTK. Further studies in invasive aspergillosis models are needed to evaluate the importance of these immunomodulatory effects.

Ovalbumin/lipopolysaccharide induced vasculitis in rats: a new predictive model

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Vandana R. Thakur ◽  
Anita A. Mehta
Keyword(s):  
Inflammatory Cytokines ◽  
Vascular Inflammation ◽  
Inflammatory Cells ◽  
Dependent Manner ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Tnf Α ◽  
Disease Induction ◽  
Dose Dependent ◽  
Different Doses

Abstract Objectives Currently, there are several animal models for vasculitis. Ovalbumin and lipopolysaccharide (OVA, LPS) are well established for causing inflammation and used as an adjunct in the vasculitis induction. However, to date, none has established the effect of OVA and LPS in disease induction. Therefore, in the present study, an attempt has been made to develop a new animal model for vasculitis using OVA/LPS in rats. Methods A total of 42 Wistar rats were divided randomly into seven groups (n=6/group), normal control, and three different doses (0.5, 1, and 5 mg/kg) of OVA and LPS treated groups. Half of the rats in each group received only intraperitoneal sensitization, while the remaining half rats were additionally subjected to a one-week intranasal challenge. Results Results showed that both OVA/LPS in their respective groups have significantly increased circulating inflammatory cells, C-reactive protein (CRP), Inflammatory cytokines (IL-1β, IL-6, TNF-α), Kidney damage markers (BUN, Creatinine), and liver function enzymes (AST, ALT) in a dose-dependent manner. Conclusions OVA/LPS induced vascular inflammation in a dose-dependent manner. However, the higher (5 mg/kg) dose of ovalbumin and lipopolysaccharide has contributed to severe vascular inflammation through increasing inflammatory cytokines. These findings suggest that OVA/LPS may contribute as a possible model for vasculitis in rats.

scholarly journals Inhibition of Complement and CD14 Attenuates the Escherichia coli-Induced Inflammatory Response in Porcine Whole Blood

2008 ◽  
Vol 77 (2) ◽  
pp. 725-732 ◽  
Author(s):  
Ebbe Billmann Thorgersen ◽  
Anne Pharo ◽  
Karin Haverson ◽  
Anne K. Axelsen ◽  
Peter Gaustad ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Inflammatory Response ◽  
Proinflammatory Cytokines ◽  
Whole Blood ◽  
Innate Immune ◽  
Dependent Manner ◽  
Bacterial Clearance ◽  
E Coli ◽  
Tnf Α ◽  
Dose Dependent

ABSTRACT The innate immune response is a double-edged sword in systemic inflammation and sepsis. Uncontrolled or inappropriate activation can damage and be lethal to the host. Several studies have investigated inhibition of downstream mediators, including tumor necrosis factor alpha (TNF-α) and interleukin-1β (IL-1β). Emerging evidence indicates that upstream inhibition is a better therapeutic approach for attenuating damaging immune activation. Therefore, we investigated inhibition of two central innate immune pathways, those of complement and CD14/Toll-like receptor 4 (TLR4)/myeloid differentiation protein 2 (MD-2), in a porcine in vitro model of Escherichia coli-induced inflammation. Porcine whole blood anticoagulated with lepuridin, which did not interfere with the complement system, was incubated with E. coli lipopolysaccharide (LPS) or whole bacteria. Inhibitors of complement and CD14 and thus the LPS CD14/TLR4/MD-2 receptor complex were tested to investigate the effect on the inflammatory response. A broad range of inflammatory readouts were used to monitor the effect. Anti-CD14 was found to saturate the CD14 molecule on granulocytes and completely inhibited LPS-induced proinflammatory cytokines in a dose-dependent manner. Anti-CD14 significantly reduced the levels of the E. coli-induced proinflammatory cytokines TNF-α and IL-1β, but not IL-8, in a dose-dependent manner. No effect on bacterial clearance was seen. Vaccinia complement control protein and smallpox inhibitor of complement enzymes, two Orthopoxvirus-encoded complement inhibitors, completely inhibited complement activation. Furthermore, these agents almost completely inhibited the expression of wCD11R3, which is associated with CD18 as a β2 integrin, on porcine granulocytes and decreased IL-8 levels significantly in a dose-dependent manner. As expected, complement inhibition reduced bacterial clearance. We conclude that inhibition of complement and CD14 attenuates E. coli-induced inflammation and might be used as a therapeutic regimen in gram-negative sepsis along with appropriate treatment with antibiotics.

scholarly journals Anti-inflammatory Effect of the Peptide LKEKK

2021 ◽  
Vol 6 (5) ◽  
Keyword(s):  
High Specificity ◽  
Dependent Manner ◽  
Thymosin Α1 ◽  
Tnf Α ◽  
Normal Human ◽  
Anti Inflammatory ◽  
Interferon Α2 ◽  
Dose Dependent

We have established that the peptide LKEKK (Np5) corresponding to the sequence 16-20 of thymosin-α1 and to the sequence 131-135 of interferon-α2, in the concentration range 50 300 µg/ear reduces in a dose-dependent manner phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced skin edema in mice .Tested in parallel peptide with inverted sequence (iNp5, KKEKL, 150-300 µg/ear) was inactive, indicating high specificity of the Np5 action. In the concentration range of 5 20 µM Np5 significantly decrease the TNF-α-induced production by normal human keranocytes of pro-inflammatory mediators IL-6 and IL-1β. Thus, Np5t has a pronounced anti-inflammatory activity in vivo and in vitro.

Mechanism of Immune System Activation by (1,4)-α-D-glucan Isolated from Tinospora cordifolia in Macrophages.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3833-3833
Author(s):  
P.K. Raveendran Nair ◽  
Steven J. Melnick ◽  
Ziad A. Khatib ◽  
Reshma Ramachandran ◽  
Enrique A. Escalon ◽  
...  
Keyword(s):  
Immune System ◽  
Inhibitory Effect ◽  
Water Soluble ◽  
Hek293 Cells ◽  
Tinospora Cordifolia ◽  
Dependent Manner ◽  
The Novel ◽  
Zymosan A ◽  
Tnf Α ◽  
Dose Dependent

Abstract We have characterized and reported the immunostimulating properties of a novel polysaccharide - (1,4)-α-D-glucan (RR1)- isolated from the medicinal plant Tinospora cordifolia [23]. This novel glucan is water soluble and having (1, 4)-α-D-glycosidic linkages in the main chain and (1, 6)-α-D-glycosidic linked side chains at an interval of 6, 7 glucose units. The signaling mechanism of the novel (1,4)-a-D-glucan (RR1) was investigated in macrophages to evaluate its immunostimulating properties. When RAW264.7 macrophages were incubated with RR1 at 4°C, the novel glucan inhibited the phagocytosis of unopsonized zymosan A bioparticles in a dose-dependent manner. RR1 also inhibited the binding and internalization of opsonized zymosan A bioparticles, although at a lower level than laminarin. Incubation of macrophages with anti-CD11b mAb followed by RR1 failed to show any inhibitory effect on RR1-induced TNF-α synthesis confirming that complement receptor 3 (CR3) is not involved in the opsonic binding and internalization of RR1 in macrophages unlike zymosan A. The anti-CD11b mAb has significant inhibitory effect on the zymosan A-induced tumor necrosis factor (TNF)-α synthesis. RR1 induced TNF-α synthesis in macrophages in a dose-dependent manner which can be completely inhibited by the NF-κB inhibitor caffeic acid phenethyl ester (CAPE) or curcumin. RR1 activated NF-κB in a time- and dose-dependent manner and this modulation of nuclear NF-κB activity is associated with the degradation of I-κB a thus facilitating the translocation of NF-κB into the nucleus. RR1-induced NF-κB activity peaks at 8 h of RR1 stimulation while I-κB a degradation occurred within 1 h of stimulation. RR1-induced NF-κB activation occurred through TLR6 signaling as evidenced by the synthesis of IL-8 in TLR6-transfected HEK293 cells. These results show that the novel (1,4)-α-D glucan from Tinospora cordifolia activates the immune system through the activation of macrophages that occurs through TLR6 signaling, NF-κB translocation and cytokine production. (Supported by Miami Children’s Hospital Foundation research funds).

scholarly journals Effect of lemon peel flavonoids on anti-fatigue and anti-oxidation capacities of exhaustive exercise mice

2020 ◽  
Vol 63 (1) ◽  
Author(s):  
Guili Bao ◽  
Yinglong Zhang ◽  
Xiaoguang Yang
Keyword(s):  
Skeletal Muscle ◽  
Superoxide Dismutase ◽  
Manganese Superoxide Dismutase ◽  
Fatty Acid Content ◽  
Hepatic Tissue ◽  
Control Group ◽  
Dependent Manner ◽  
Lemon Peel ◽  
Tnf Α ◽  
Dose Dependent

AbstractIn this study, lemon peel flavonoids (LPF) were administered to investigate its effect on the anti-fatigue and antioxidant capacity of mice that undergo exercise until exhaustion. LPF (88.36 min in LPFH group mice) significantly increased the exhaustion swimming time compare to the untreated mice (40.36 min), increased the liver glycogen and free fatty acid content in mice and reduce lactic acid and BUN content in a dose-dependent manner. As the concentration of lemon peel flavonoids increased, the serum creatine kinase, aspartate aminotransferase, and alanine aminotransferase levels of mice gradually decreased. LPF increases superoxide dismutase (SOD) and catalase (CAT) levels in mice and reduces malondialdehyde levels in a dose-dependent manner. And LPF raises hepatic tissue SOD, CAT activities and reduces skeletal muscle tissue iNOS, TNF-α levels of mice compared to the control group. LPF also enhanced the expression of copper/zinc-superoxide dismutase (Cu/Zn-SOD), manganese-superoxide dismutase (Mn-SOD), and CAT mRNA in mouse liver tissue. LPF also enhanced the expression of alanine/serine/cysteine/threonine transporter 1 (ASCT1) mRNA and attenuate the expression of syncytin-1, inducible nitric oxide synthase (iNOS), and tumor necrosis factor (TNF)-α in mouse skeletal muscle. According to high-performance liquid chromatography (HPLC) analysis, it was found that LPF contains flavonoids such as rutin, astragalin, isomangiferin, naringin, and quercetin. Our experimental data show that LPF has good anti-fatigue effects and anti-oxidation ability. In summary, LPF has high prospects to be developed and added to nutritional supplements.

scholarly journals Silica nanoparticles induce NLRP3 inflammasome activation in human primary immune cells

2017 ◽  
Vol 23 (8) ◽  
pp. 697-708 ◽  
Author(s):  
Diana M Gómez ◽  
Silvio Urcuqui-Inchima ◽  
Juan C Hernandez
Keyword(s):  
Physicochemical Properties ◽  
Silica Nanoparticles ◽  
Inflammatory Cytokines ◽  
Nlrp3 Inflammasome ◽  
Deep Understanding ◽  
Inflammasome Activation ◽  
Dependent Manner ◽  
Dose Dependent ◽  
Pro Inflammatory Cytokines

In recent years, the potential use of silica nanoparticles (SiNPs) among different biomedical fields has grown. A deep understanding of the physicochemical properties of nanoparticles (NPs) and their regulation of specific biological responses is crucial for the successful application of NPs. Exposure to NP physicochemical properties (size, shape, porosity, etc.) could result in deleterious effects on cellular functions, including a pro-inflammatory response mediated via activation of the NLRP3 inflammasome. The aim of this study was to evaluate the potential in vitro immunomodulatory effect of 12-nm and 200-nm SiNPs on the expression of pro-inflammatory cytokines and NLRP3 inflammasome components in human primary neutrophils and PBMCs. This study demonstrates that regardless of the size of the nanoparticles, SiNPs induce the production of pro-inflammatory cytokines in a dose-dependent manner. Induced IL-1β production after exposure to SiNPs suggests the involvement of NLRP3 inflammasome components participation in this process. In conclusion, SiNPs induce the production of pro-inflammatory cytokines in a dose-dependent manner. Furthermore, our data suggest that the production and release of IL-1β possibly occurs through the formation of the NLRP3 inflammasome.

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