Cutaneous glucocorticoid receptor sensitivity and pro-inflammatory cytokine levels in antidepressant-resistant depression

2005 ◽  
Vol 36 (1) ◽  
pp. 37-43 ◽  
Author(s):  
PETER FITZGERALD ◽  
SINEAD M. O'BRIEN ◽  
PAUL SCULLY ◽  
KIM RIJKERS ◽  
LUCINDA V. SCOTT ◽  
...  
Keyword(s):  
Glucocorticoid Receptor ◽  
Inflammatory Cytokines ◽  
Topical Steroid ◽  
Depression Scale ◽  
Topical Steroids ◽  
Hamilton Depression Scale ◽  
Tnf Α ◽  
Resistant Depression ◽  
The Impact ◽  
Pro Inflammatory Cytokines

Background. There is evidence to indicate that peripheral glucocorticoid receptor (GR) function is reduced in major depression, and a possible molecular explanation for this is the impact of raised pro-inflammatory cytokines. The topical steroid vasoconstriction assay provides a convenient probe of peripheral GR function. The present study sought to assess the sensitivity of peripheral GRs in antidepressant-resistant major depressives and investigate the association between GR sensitivity and circulating plasma cytokines.Method. Nineteen antidepressant-resistant depressives together with age- and sex-matched healthy controls underwent the steroid vasoconstriction assay using three commercial preparations of corticosteroids containing clobetasol propionate 0·05%, betamethasone valerate 0·1%, and clobetasone butyrate 0·05%, corresponding to very potent, potent, and moderately potent steroid creams respectively. The pro-inflammatory cytokines, tumour necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) were measured using enzyme-linked immunosorbent assays. The severity of the depressive episode was assessed using the Hamilton Depression Scale (HAMD).Results. Depressed subjects had a significantly reduced vasoconstriction response across all three strengths of steroid. They also had significantly higher concentrations of TNF-α and IL-6. There was a significant inverse correlation between TNF-α concentration and vasoconstriction response and also between the HAMD score and vasoconstriction response.Conclusions. These findings suggest that cutaneous GR function is abnormal in antidepressant-resistant depression, that circulating TNF-α may play a significant role in this abnormality and that the efficacy of topical steroids in antidepressant-resistant depressives is reduced.

scholarly journals The FcγRIII Engagement Augments PMA-Stimulated Neutrophil Extracellular Traps (NETs) Formation by Granulocytes Partially via Cross-Talk between Syk-ERK-NF-κB and PKC-ROS Signaling Pathways

Biomedicines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1127
Author(s):  
Cheng-Hsun Lu ◽  
Ko-Jen Li ◽  
Cheng-Han Wu ◽  
Chieh-Yu Shen ◽  
Yu-Min Kuo ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Inflammatory Cytokines ◽  
Cross Talk ◽  
Neutrophil Extracellular Traps ◽  
Ros Generation ◽  
Dependent Manner ◽  
Extracellular Traps ◽  
Tnf Α ◽  
The Impact ◽  
Pro Inflammatory Cytokines

Polymorphonuclear neutrophils (PMNs) are the most abundant white blood cell in the circulation capable of neutrophil extracellular traps (NETs) formation after stimulation. Both NADPH oxidase-dependent and -independent pathways are involved in NET formation. The IgG is the most abundant immunoglobulin in human serum. However, the impact of the circulating IgG on NET formation is totally unexplored. In this study, the all-trans retinoic acid (ATRA)-induced mature granulocytes (dHL-60) were pre-treated with monomeric human IgG, papain-digested Fab fragment, crystallizable IgG Fc portion, rituximab (a human IgG1), or IgG2. The NET formation of the dHL-60 in the presence/absence of phorbol 12-myristate 13-acetate (PMA) stimulation was then measured by the fluorescent area after SYTOX green nucleic acid stain. The intracellular reactive oxygen species (ROS) generation was measured by flow cytometry. Total and phosphorylated Syk, SHP-1, and ERK were detected by immunoblot. We found that human monomeric IgG and its subclasses IgG1 and IgG2 per se induced negligible NET formation of dHL-60, but the FcγRIII engagement by these IgG subclasses and Fc portion augment PMA-stimulated dHL-60 NET formation in a dose-dependent manner. Furthermore, we found that increased Syk and ERK phosphorylation, intracellular ROS generation, and pro-inflammatory cytokines, IL-8 and TNF-α, production could be induced after FcγRIII engagement. Blocking FcγRIII engagement by a specific antibody diminished the augmented NET formation. In conclusion, we discovered that cross-talk between FcγRIII engagement-induced Syk-ERK and PMA-induced PKC signaling pathways augment NET formation of dHL-60 via increased ROS generation and pro-inflammatory cytokines, IL-8 and TNF-α, production.

scholarly journals Immunomodulatory Effect of Vitamin C on Proinflammatory Cytokines Production in Ossimi Lambs (Ovis aries) with Pneumonic Pasteurellosis

Animals ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 3374
Author(s):  
Mohamed Abdo Rizk ◽  
Shimaa Abd El-Salam El-Sayed ◽  
Doaa Salman ◽  
Basma H. Marghani ◽  
Hossam Elshahat Gadalla ◽  
...  
Keyword(s):  
Vitamin C ◽  
Inflammatory Cytokines ◽  
Interleukin 1 ◽  
Serum Levels ◽  
Ovis Aries ◽  
Necrosis Factor Alpha ◽  
Pneumonic Pasteurellosis ◽  
Tnf Α ◽  
The Impact ◽  
Pro Inflammatory Cytokines

In this study, we have investigated the impact of vitamin C on the production of pro-inflammatory cytokines (interleukin 1 β (IL-1 β), interleukin 6 (IL-6), interleukin 12p40 (IL-12p40), interferon gamma (IFNγ), and tumor necrosis factor alpha (TNF-α)) in lambs naturally infected by pneumonic pasteurellosis. Of 37 lambs, 18 lambs were identified to have pneumonic pasteurellosis and randomly allocated into two equal groups. Single subcutaneous dose of tulathromycine alone (2.5 mg kg−1) or tulathromycine combined with vitamin C (3 gm kg−1) were administrated to the diseased lambs. The serum levels of IL-1β, IL-6, IFN-γ, and TNF-α were returned to the normal levels in pneumonic lambs treated with the combination therapy. The obtained results indicate the selective influences of vitamin C on pro-inflammatory cytokines production in sera of lambs with pneumonic pasteurellosis and highlights the value of vitamin C as a potential anti-inflammatory drug and ideal immunomodulatory agent.

scholarly journals Brain-Derived Neurotropic Factor (BDNF) Mediates the Protective Effect of L.Cucurbita Pepo on Salivary Glands of Depressed Rat Evident by Structural, Biochemical and Molecular Study

2021 ◽  
Author(s):  
Hailah M. ALmohaimeed ◽  
Emad A. Albadawi ◽  
Zuhair M. Mohammedsaleh ◽  
Hadel M. Alghabban ◽  
Hanan S. Seleem ◽  
...  
Keyword(s):  
Salivary Glands ◽  
Inflammatory Cytokines ◽  
Serum Levels ◽  
Albino Rats ◽  
Mild Stress ◽  
Ductal Cells ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
The Impact ◽  
Pro Inflammatory Cytokines

Abstract BackgroundAcute and chronic stresses affect the salivary glands which are the source of plasma BDNF during stressful conditions. Pumpkin is a medicinal plant with an evident antioxidant, anti-inflammatory and potential antidepressant effects. This work was conducted to assess the impact of chronic unpredictable mild stress (CUMS) on the structure of albino rats’ salivary glands and evaluate the role of pumpkin extract (Pump) in ameliorating this effect. MethodsFour groups (n=10 each) of male albino rats included in this study; the control, CUMS, CUMS+fluoxetine and (CUMS+Pump). Corticosterone, pro-inflammatory cytokines (TNF-α & IL-6) and the oxidant/antioxidant profile were all assessed in the serum. BDNF mRNA level was measured in the salivary glands using qRT-PCR. Histopathological changes of the salivary glands were also assessed. ResultsDepression was confirmed behaviorally and biochemically. Exposure to CUMS significantly (p< 0.001) up-regulated the level of serum corticosterone. CUMS induced degenerative changes in the secretory and ductal system, atrophy of acini and increased apoptosis of the acinar and ductal cells. Both fluoxetine and Pump significantly up-regulated (p<0.001) BDNF expression in the salivary glands and ameliorated the CUMS-induced histopathological alterations in the salivary glands. Pumpkin significantly (p<0.001) increased the serum levels of antioxidant enzymes SOD, GPX and CAT and reduced the serum levels of the pro-inflammatory cytokines TNF-α, IL-6.ConclusionPumpkin ameliorates chronic stress-induced depression in rats by exerting a promising anti-inflammatory, antioxidant and anti-depressant-like effects in rats exposed to CUMS. Pump subsequently improved stress-induced structural changes in the salivary glands that might be due to the glands up-regulation of BDNF expression.Trial registrationNot applicable.

scholarly journals Hindlimb unloading causes regional loading-dependent changes in osteocyte inflammatory cytokines that are modulated by exogenous irisin treatment

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Corinne E. Metzger ◽  
S. Anand Narayanan ◽  
Peter H. Phan ◽  
Susan A. Bloomfield
Keyword(s):  
Bone Loss ◽  
Bone Turnover ◽  
Inflammatory Cytokines ◽  
Cancellous Bone ◽  
Proximal Humerus ◽  
Bone Volume ◽  
Hindlimb Unloading ◽  
Tnf Α ◽  
The Impact ◽  
Pro Inflammatory Cytokines

Abstract Disuse-induced bone loss is characterized by alterations in bone turnover. Accruing evidence suggests that osteocytes respond to inflammation and express and/or release pro-inflammatory cytokines; however, it remains largely unknown whether osteocyte inflammatory proteins are influenced by disuse. The goals of this project were (1) to assess osteocyte pro-inflammatory cytokines in the unloaded hindlimb and loaded forelimb of hindlimb unloaded rats, (2) to examine the impact of exogenous irisin during hindlimb unloading (HU). Male Sprague Dawley rats (8 weeks old, n = 6/group) were divided into ambulatory control, HU, and HU with irisin (HU + Ir, 3×/week). Lower cancellous bone volume, higher osteoclast surfaces (OcS), and lower bone formation rate (BFR) were present at the hindlimb and 4th lumbar vertebrae in the HU group while the proximal humerus of HU rats exhibited no differences in bone volume, but higher BFR and lower OcS vs. Con. Osteocyte tumor necrosis factor-α (TNF-α), interleukin-17 (IL-17), RANKL, and sclerostin were elevated in the cancellous bone of the distal femur of HU rats vs. Con, but lower at the proximal humerus in HU rats vs. Con. Exogenous irisin treatment increased BFR, and lowered OcS and osteocyte TNF-α, IL-17, RANKL, and sclerostin in the unloaded hindlimb of HU + Ir rats while having minimal changes in the humerus. In conclusion, there are site-specific and loading-specific alterations in osteocyte pro-inflammatory cytokines and bone turnover with the HU model of disuse bone loss, indicating a potential mechanosensory impact of osteocyte TNF-α and IL-17. Additionally, exogenous irisin significantly reduced the pro-inflammatory status of the unloaded hindlimb.

Impact of point-of-care testing and treatment of sexually transmitted infections and bacterial vaginosis on genital tract inflammatory cytokines in a cohort of young South African women

2021 ◽  
pp. sextrans-2020-054740
Author(s):  
Nigel Garrett ◽  
Andile Mtshali ◽  
Farzana Osman ◽  
Lindi Masson ◽  
Lyle R McKinnon ◽  
...  
Keyword(s):  
South African ◽  
Inflammatory Cytokines ◽  
Point Of Care ◽  
Principal Component ◽  
African Women ◽  
Tnf Α ◽  
Vaginal Health ◽  
South African Women ◽  
The Impact ◽  
Pro Inflammatory Cytokines

ObjectivesSTIs cause inflammation that is detrimental for both HIV risk and reproductive health. We assessed the impact of point-of-care (POC) STI testing, immediate treatment and expedited partner therapy (EPT) on genital tract cytokines among a cohort of young South African women.MethodsHIV-negative women underwent POC testing for Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) and Trichomonas vaginalis (TV) by Xpert CT/NG and OSOM TV, and for bacterial vaginosis (BV) by microscopy. Women with STIs and/or BV received immediate treatment, EPT for STIs and retested after 6 and 12 weeks. Concentrations of 48 cytokines were measured in cervicovaginal fluid at each visit using multiplex ELISA technology. The impact of STI treatment on cytokine concentrations was assessed by multivariable linear mixed models and principal component analysis.ResultsThe study enrolled 251 women with median age of 23 years (IQR 21–27). The prevalence of CT, NG and TV were 14.3%, 4.4% and 4.0%, and 34.3% had BV. Women with STIs or BV at baseline (n=94) had significantly higher concentrations of pro-inflammatory cytokines (interleukin (IL)-1α, IL-1β, IL-6, tumour necrosis factor (TNF)-α, TNF-β, IL-18 and macrophage inflammatory factor (MIF)) and chemokines (IL-8, IL-16, macrophage inflammatory protein (MIP)-1α, IFN-α2, monokine induced by gamma interferon (MIG), monocyte chemoattractant protein (MCP)-3, regulated on activation normal T cell expressed and secreted and eotaxin) compared with women without (n=157). STI treatment was strongly associated with reduced concentrations of pro-inflammatory cytokines IL-6 (p=0.004), IL-1β (p=0.013), TNF-α (p=0.018) and chemokines MIG (p=0.008) and growth-related oncogene (GRO)-α (p=0.025). A lower Nugent score was associated with a reduction in pro-inflammatory cytokines IL-1α (p=0.003), TNF-related apoptosis-inducing ligand (p=0.004), MIF (p=0.010) and IL-18 (p<0.001), but an increase in chemokines MIG (p=0.020), GRO-α (p<0.001), IP-10 (p<0.001), MIP-1β (p=0.008) and MCP-1 (p=0.005). Principal component analysis showed differences in STI and BV-related inflammatory profiles, but that resolution restored a profile consistent with vaginal health.ConclusionsA comprehensive STI intervention effectively reduced genital inflammation among young women, thereby improving vaginal health and potentially reducing HIV risk.

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 Punicalagin Prevents Inflammation in LPS-Induced RAW264.7 Macrophages by Inhibiting FoxO3a/Autophagy Signaling Pathway

Nutrients ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 2794 ◽  
Author(s):  
Cao ◽  
Chen ◽  
Ren ◽  
Zhang ◽  
Tan ◽  
...  
Keyword(s):  
Western Blot ◽  
Signaling Pathway ◽  
Inflammatory Cytokines ◽  
Blot Analysis ◽  
Western Blot Analysis ◽  
Inflammatory Responses ◽  
Raw264.7 Macrophages ◽  
Tnf Α ◽  
Autophagy Inhibition ◽  
Pro Inflammatory Cytokines

Punicalagin, a hydrolysable tannin of pomegranate juice, exhibits multiple biological effects, including inhibiting production of pro-inflammatory cytokines in macrophages. Autophagy, an intracellular self-digestion process, has been recently shown to regulate inflammatory responses. In this study, we investigated the anti-inflammatory potential of punicalagin in lipopolysaccharide (LPS) induced RAW264.7 macrophages and uncovered the underlying mechanisms. Punicalagin significantly attenuated, in a concentration-dependent manner, LPS-induced release of NO and decreased pro-inflammatory cytokines TNF-α and IL-6 release at the highest concentration. We found that punicalagin inhibited NF-κB and MAPK activation in LPS-induced RAW264.7 macrophages. Western blot analysis revealed that punicalagin pre-treatment enhanced LC3II, p62 expression, and decreased Beclin1 expression in LPS-induced macrophages. MDC assays were used to determine the autophagic process and the results worked in concert with Western blot analysis. In addition, our observations indicated that LPS-induced releases of NO, TNF-α, and IL-6 were attenuated by treatment with autophagy inhibitor chloroquine, suggesting that autophagy inhibition participated in anti-inflammatory effect. We also found that punicalagin downregulated FoxO3a expression, resulting in autophagy inhibition. Overall these results suggested that punicalagin played an important role in the attenuation of LPS-induced inflammatory responses in RAW264.7 macrophages and that the mechanisms involved downregulation of the FoxO3a/autophagy signaling pathway.

scholarly journals Evaluation of the online-based self-help programme “Selfapy” in patients with unipolar depression: study protocol for a randomized, blinded parallel group dismantling study

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Rico Krämer ◽  
Stephan Köhler
Keyword(s):  
Depressive Symptoms ◽  
Depression Scale ◽  
Drop Out ◽  
Control Group ◽  
Hamilton Depression Scale ◽  
Online Interventions ◽  
Phone Calls ◽  
Self Help ◽  
Low Threshold ◽  
The Impact

Abstract Background Patients with mild to moderate depressive symptoms can have limited access to regular treatment; to ensure appropriate care, low-threshold treatment is needed. Effective online interventions could increase the supply of low-threshold treatment. Further research is needed to evaluate the effectiveness of online interventions. This study aims to evaluate the online-based self-help programme “Selfapy” on a sample of depressive subjects and compares the impact of the programme’s unaccompanied version with its therapeutic accompanied version. Methods A sample of 400 subjects that have a mild to severe depressive episode (Becks Depression Inventory - II and Hamilton Depression Scale) will be used. Subjects are randomly assigned to immediate access to an unaccompanied course (no support from psychologist via weekly phone calls), immediate access to an accompanied course (support from a psychologist via weekly phone calls) or a waiting list control group (access to the intervention after 24 weeks). The intervention will last for a period of 12 weeks. Depressive symptoms as a primary parameter, as well as various secondary parameters, such as life satisfaction, therapeutic relationships, social activation, self-esteem, attitudes towards Internet interventions and drop-out rates, are recorded at four different points in time: at baseline (T1), 6 weeks after the start of the intervention (T2), 12 weeks after the start of the intervention (T3) and 3 months after completion of the treatment follow-up (T4). Conclusion This randomized and controlled, blinded study will make use of a “dismantled” approach to adequately compare the accompanied and unaccompanied versions of the intervention. Positive and meaningful results are expected that could influence the acceptance and implementation of online interventions. Trial registration German Clinical Trials Register DRKS00017191. Registered on 14 June 2019

scholarly journals Modulation of ACE-2 mRNA by inflammatory cytokines in human thyroid cells: a pilot study

Endocrine ◽  
2021 ◽  
Author(s):  
Francesca Coperchini ◽  
Gianluca Ricci ◽  
Laura Croce ◽  
Marco Denegri ◽  
Rubina Ruggiero ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Combination Treatment ◽  
Primary Cultures ◽  
Human Thyroid ◽  
Thyroid Cell ◽  
Mrna Levels ◽  
Thyroid Cells ◽  
Tnf Α ◽  
Ifn Γ ◽  
Pro Inflammatory Cytokines

Abstract Introduction Angiotensin-converting-enzyme-2 (ACE-2) was demonstrated to be the receptor for cellular entry of SARS-CoV-2. ACE-2 mRNA was identified in several human tissues and recently also in thyroid cells in vitro. Purpose Aim of the present study was to investigate the effect of pro-inflammatory cytokines on the ACE-2 mRNA levels in human thyroid cells in primary cultures. Methods Primary thyroid cell cultures were treated with IFN-γ and TNF-α alone or in combination for 24 h. ACE-2 mRNA levels were measured by RT-PCR. As a control, the levels of IFN-γ inducible chemokine (CXCL10) were measured in the respective cell culture supernatants. Results The mean levels of ACE-2 mRNA increased after treatment with IFN-γ and TNF-α in all the thyroid cell preparations, while the combination treatment did not consistently synergically increase ACE-2-mRNA. At difference, CXCL10 was consistently increased by IFN-γ and synergically further increased by the combination treatment with IFN-γ + TNF-α, with respect to IFN-γ alone. Conclusions The results of the present study show that IFN-γ and, to a lesser extent TNF-α consistently increase ACE-2 mRNA levels in NHT primary cultures. More interestingly, the combined stimulation (proven to be effective according to the synergic effect registered for CXCL10) produces different responses in terms of ACE-2 mRNA modulation. These results would suggest that elevated levels of pro-inflammatory cytokines could facilitate the entering of the virus in cells by further increasing ACE-2 expression and/or account for the different degree of severity of SARS-COV-2 infection. This hypothesis deserves to be confirmed by further specific studies.

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