Mutations in GBA and LRRK2 Are Not Associated with Increased Inflammatory Markers

Background: Inflammation is an integral part of neurodegeneration including in Parkinson’s disease (PD). Ashkenazi Jews have high rates of genetic PD with divergent phenotypes among GBA-PD and LRRK2-PD. The role of inflammation in the prodromal phase of PD and the association with disease phenotype has yet to be elucidated. Objective: To assess central and peripheral cytokines among PD patients with mutations in the LRRK2 and GBA genes and among non-manifesting carriers (NMC) of these mutations in order to determine the role of inflammation in genetic PD. Methods: The following cytokines were assessed from peripheral blood and cerebrospinal fluid (CSF): TNF-α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10 and INF- γ. A comprehensive intake including general medical conditions, use of anti-inflammatory treatments, motor and cognitive assessments and additional laboratory measures were recorded, enabling the construction of the MDS probable prodromal score. Results: Data from 362 participants was collected: 31 idiopathic PD (iPD), 30 LRRK2-PD, 77 GBA-PD, 3 homozygote GBA-PD, 3 GBA-LRRK2-PD, 67 LRRK2-NMC, 105 GBA-NMC, 14 LRRK2-GBA-NMC, and 32 healthy controls. No between-group differences in peripheral or CSF cytokines were detected. No correlation between disease characteristics or risk for prodromal PD could be associated with any inflammatory measure. Conclusion: In this study, we could not detect any evidence on dysregulated immune response among GBA and LRRK2 PD patients and non-manifesting mutation carriers.

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TNF-α Activating Osteoclasts in Patients with Psoriatic Arthritis Enhances the Recruitment of Osteoclast Precursors: A Plausible Role of WNT5A-MCP-1 in Osteoclast Engagement in Psoriatic Arthritis

International Journal of Molecular Sciences ◽

10.3390/ijms23020921 ◽

2022 ◽

Vol 23 (2) ◽

pp. 921

Author(s):

Shang-Hung Lin ◽

Ji-Chen Ho ◽

Sung-Chou Li ◽

Yu-Wen Cheng ◽

Chung-Yuan Hsu ◽

...

Keyword(s):

Psoriatic Arthritis ◽

Rna Interference ◽

Joint Destruction ◽

Neutralizing Antibody ◽

Healthy Controls ◽

Osteoclast Precursors ◽

Tnf Α ◽

Wnt Ligands

Psoriatic arthritis (PsA) results from joint destruction by osteoclasts. The promising efficacy of TNF-α blockage indicates its important role in osteoclastogenesis of PsA. WNT ligands actively regulate osteoclastogenesis. We investigated how WNT ligands activate osteoclasts amid the TNF-α milieu in PsA. We first profiled the expression of WNT ligands in CD14+ monocyte-derived osteoclasts (MDOC) from five PsA patients and five healthy controls (HC) and then validated the candidate WNT ligands in 32 PsA patients and 16 HC. Through RNA interference against WNT ligands in MDOC, we determined the mechanisms by which TNF-α exerts its effects on osteclastogenesis or chemotaxis. WNT5A was selectively upregulated by TNF-α in MDOC from PsA patients. The number of CD68+WNT5A+ osteoclasts increased in PsA joints. CXCL1, CXCL16, and MCP-1 was selectively increased in supernatants of MDOC from PsA patients. RNA interference against WNT5A abolished the increased MCP-1 from MDOC and THP-1-cell-derived osteoclasts. The increased migration of osteoclast precursors (OCP) induced by supernatant from PsA MDOC was abolished by the MCP-1 neutralizing antibody. WNT5A and MCP-1 expressions were decreased in MDOC from PsA patients treated by biologics against TNF-α but not IL-17. We conclude that TNF-α recruits OCP by increased MCP-1 production but does not directly activate osteoclastogenesis in PsA.

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Physiological persona differences based on stress and inflammation between meditators and healthy controls

Journal of Complementary and Integrative Medicine ◽

10.1515/jcim-2019-0106 ◽

2019 ◽

Vol 17 (2) ◽

Cited By ~ 1

Author(s):

Dipti Magan ◽

Raj Kumar Yadav

Keyword(s):

Blood Pressure ◽

Body Mass Index ◽

Plasma Levels ◽

Inflammatory Markers ◽

Tumor Necrosis ◽

Healthy Controls ◽

Short Term ◽

Tnf Α ◽

Necrosis Factor

AbstractBackgroundNowadays, yoga is endorsed and advised routinely to stay fit and healthy, as well as control many chronic diseases including diabetes type 2, hypertension, coronary artery diseases, etc. Now, our assumption is that those who do regular yoga have different persona than who do not do yoga regularly. We planned to test our hypothesis scientifically, and therefore baseline physiological characteristics with stress and inflammation levels in long-term and short-term meditators and healthy novice controls were analyzed.MethodsIn this retrospective analysis, 97 male participants were included for their Baseline analysis. Fifteen apparently healthy subjects practicing preksha meditation (since >5 years, at least 5 days a week) were included as long-term meditators (LTMs); 58 subjects who attended one of our short-term yoga-based lifestyle intervention programs for 2 weeks were included as short-term meditators (STMs); 24 male novice subjects, who did not participate in any yogic intervention, were included as healthy controls. Here, we analyzed the Baseline plasma levels of stress and inflammatory markers, cortisol, β-endorphin, interleukin (IL)-6 and tumor necrosis factor (TNF)-α in long-term meditators vs. short-term meditators vs. healthy controls.Outcome measuresThe study parameters body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), plasma levels of stress and immune markers, cortisol, β-endorphin (β-Ed), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), were assessed in all the three groups at baseline.ResultsSignificant (p<0.05) differences were observed at baseline for plasma levels of stress and inflammatory markers as well as body mass index and systolic blood pressure among LTM vs. STM vs. healthy controls.ConclusionsOur observations suggest that the subjects who do regular yoga-meditation practice have better stress & inflammation status than comparable age matched healthy controls.

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Non-alcoholic steatohepatitis patients exhibit reduced CD47, and increased sphingosine, cholesterol and MCP1 levels in the erythrocyte membranes

10.1101/2022.01.12.22269197 ◽

2022 ◽

Author(s):

Charalampos Papadopoulos ◽

Eleftheria Spourita ◽

Konstantinos Mimidis ◽

George Kolios ◽

Ioannis Tentes ◽

...

Keyword(s):

Erythrocyte Membrane ◽

Metabolic Reprogramming ◽

Erythrocyte Membranes ◽

Healthy Controls ◽

Alcoholic Steatohepatitis ◽

Tnf Α ◽

Liver Transplantations ◽

Cause Of Deaths ◽

Layer Chromatography

Non-alcoholic steatohepatitis (NASH) constitutes a significant cause of deaths, liver transplantations and economic costs worldwide. Despite extended research, investigations on the role of erythrocytes are scarce. Red blood cells from experimental animals and human patients with NASH, present phosphatidylserine exposure which is then recognized by Kupffer cells. This event leads to erythrophagocytosis, and amplification of inflammation through iron disposition. In addition, it has been shown that erythrocytes from NASH patients release the chemokine MCP1, leading to increased TNF-α release from macrophages RAW 264.7. However, erythrophagocytosis can also be caused by reduced CD47 levels. In addition, increased MCP1 release could be either signal-induced, or caused by higher MCP1 levels on the erythrocyte membrane. Finally, erythrocyte efferocytosis could provide additional inflammatory metabolites. In this study, we measured the erythrocyte membrane levels of CD47 and MCP1 by ELISA, and cholesterol and sphingosine with thin-layer chromatography. 18 patients (8 men, 10 women aged 56.7+/-11.5 years) and 14 healthy controls (7 men, 7 women aged 39.3+/-15.5 years) participated in our study. The erythrocyte CD47 levels were decreased in the erythrocyte membranes of NASH patients (844+/-409 pg/ml) compared to healthy controls (2969+/-1936 pg/ml) with P(Healthy>NAFLD)=99.1%, while the levels of MCP1 were increased in NASH patients (389+/-255 pg/ml), compared to healthy controls (230+/-117 pg/ml) with P(Healthy<NAFLD)=88.9%. Moreover, in erythrocyte membranes there was a statistically significant accumulation of sphingosine and cholesterol in NASH patients, compared to healthy controls. Our results imply that erythrocytes release chemotactic (find me signals) MCP1, while containing reduced (do not eat me signals) CD47. These molecules can lead to erythrophagocytosis. Next, increased (goodbye signals) sphingosine and cholesterol could augment inflammation by metabolic reprogramming.

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Role of cytokines and other prophetic variables in the development and progression of disease in patients suffering from COVID-19

10.1101/2020.10.28.20221408 ◽

2020 ◽

Author(s):

Arif Malik ◽

Saima Iqbal ◽

Sulayman Waquar ◽

Muhammad Mansoor Hafeez

Keyword(s):

Inflammatory Markers ◽

Medical Practitioner ◽

Serum Samples ◽

Necrosis Factor Alpha ◽

Enveloped Virus ◽

Global Pandemic ◽

Tnf Α ◽

Causative Agents ◽

Progression Of Disease

ABSTRACTINTRODUCTIONOutbreak of the novel COVID-19 infection identifies both causative agents that threaten global pandemic in 2003 and 2011. It is an enveloped virus with spike (S) protein attached that facilitates its receptor binding on the surface. Although it has brought about the global interest for the researchers and medical practitioner in the identification of potential targets that may be addressed in order to cope up with the situation. In the current study potential role of cytokines and related inflammatory markers have been identified that interplays in the progression of disease in COVID-19 patients.MATERIALS AND METHODSCurrent study substitutes hundred and fifty (n=150) patients with novel-COVID-19 and hundred (n=100) healthy controls. After getting informed consent serum samples of the participants were collected and analyzed for their significance in the disease progression. Levels of Interleukins i.e., (IL- 1,6,8,10,11) and tumor necrosis factor-alpha (TNF-α) were determined with help of their specific spectrophotometric and ELISA methods.RESULTSFindings of study show significant increase in the levels of interleukins and TNF-α that signifies the presence of “cytokine storm” in worsening the condition in respect to the exposure of COVID-19. Levels of IL-1 and 6 were significantly higher in patients (98.69±39.35pg/ml and 71.95±28.41 pg/ml) as compared to controls (30.06±14.19pg/ml and 9.46±3.43pg/ml) where, (p=0.001 and 0.007). It also suggests that IL-6 is most sensitive test with about (98%) sensitivity in comparison with 96%,95%, 95%,93% and 92% in case of IL-10,1,8,11 and TNF-α respectively.CONCLUSIONCurrent study elucidate the effects of cytokines and respective inflammatory markers in the progression of the COVID-19. Findings show that activation of macrophages and neutrophils have significant role in the worsening of the symptoms and progression of the viral infection. Thus, use of certain blockers in initial stages could serve with potent benefits in coping up the infectious condition.

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Lonomia obliqua Venom Induces NF-κB Activation and a Pro-Inflammatory Profile in THP-1-Derived Macrophage

Toxins ◽

10.3390/toxins13070462 ◽

2021 ◽

Vol 13 (7) ◽

pp. 462

Author(s):

Douglas Oliveira ◽

Jean Gabriel de Souza ◽

Miryam Alvarez-Flores ◽

Priscila Cunegundes ◽

Carlos DeOcesano-Pereira ◽

...

Keyword(s):

Inflammatory Markers ◽

Cytotoxic Effect ◽

Clinical Manifestations ◽

Release Profile ◽

Coagulation Cascade ◽

Tnf Α ◽

System Components ◽

Inflammatory Profile ◽

Lonomia Obliqua

Envenomation caused by contact with Lonomia obliqua bristles is characterized by pain, an intense systemic proinflammatory reaction and disturbances in the coagulation cascade that can cause severe clinical manifestations and death. However, the role of immune system components in these effects is still poorly understood. In this study, we evaluated the cytotoxic effect of L. obliqua venom on THP-1-derived macrophages and its ability to modulate inflammatory markers, as well as the cytokine and chemokine release profile. Our results show that L. obliqua venom is able to directly exert a potent pro-inflammatory reaction in macrophages, characterized by the activation of the NF-κB transcription factor pathway, the expression of CD80 and CD83, and the release of pro-inflammatory mediators such as TNF-α, IL-1β, IL-6, IL-8 and CXCL10. These results suggest that macrophages can play an important role during the orchestration of the inflammatory response present in envenomation caused by Lonomia obliqua caterpillars.

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Effect of AT1 receptor antagonism on vascular and circulating inflammatory mediators in SHR: role of NF-κB/IκB system

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.01061.2003 ◽

2005 ◽

Vol 288 (1) ◽

pp. H111-H115 ◽

Cited By ~ 87

Author(s):

David Sanz-Rosa ◽

M. Pilar Oubiña ◽

Eva Cediel ◽

Natalia de las Heras ◽

Onofre Vegazo ◽

...

Keyword(s):

Blood Pressure ◽

Angiotensin Ii ◽

Mrna Expression ◽

Inflammatory Mediators ◽

Plasma Levels ◽

Inflammatory Markers ◽

Angiotensin Ii Receptor ◽

Tnf Α ◽

Wistar Kyoto

We investigated the role of angiotensin II in vascular and circulating inflammatory markers in spontaneously hypertensive rats (SHR). IL-1β, IL-6, and TNF-α aortic mRNA expression and plasma levels were measured in adult SHR untreated or treated with the angiotensin II receptor antagonist candesartan (2 mg·kg−1·day−1) or antihypertensive triple therapy (TT; in mg·kg−1·day−1: 20 hydralazine + 7 type 1 hydrochlorothiazide + 0.15 reserpine) for 10 wk. Likewise, aortic expression of NF-κB p50 subunit precursor p105 and its inhibitor (IκB) were measured. Age-matched Wistar-Kyoto rats (WKY) served as normotensive reference. High blood pressure levels were associated with increased ( P < 0.05) aortic mRNA expression of IL-1β, IL-6, and TNF-α. Hypertension was also accompanied by increased IL-1β and IL-6 plasma levels. No differences were observed in circulating TNF-α levels between SHR and WKY. SHR presented elevated aortic mRNA expression of the transcription factor NF-κB and reduction in its inhibitor, IκB. Candesartan decreased ( P < 0.05) blood pressure levels, aortic mRNA expression of IL-1β, IL-6, and TNF-α, and ( P < 0.05) IL-1β and IL-6 plasma concentration. However, although arterial pressure decrease was comparable for the treatments, TT only partially reduced the increments in inflammatory markers. In fact, candesartan-treated rats showed significantly lower levels of circulating and vascular inflammatory markers than TT-treated animals. The treatments increased IκB mRNA expression similarly. However, only candesartan reduced NF-κB mRNA expression. In summary, 1) SHR presented a vascular inflammatory process; 2) angiotensin II, and increased hemodynamic forces associated with hypertension, seems to be involved in stimulation of inflammatory mediators through NF-κB system activation; and 3) reduction of inflammatory mediators produced by candesartan in SHR could be partially due to both downregulation of NF-κB and upregulation of IκB.

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Systemic Oxidative Stress and Conversion to Dementia of Elderly Patients with Mild Cognitive Impairment

BioMed Research International ◽

10.1155/2014/309507 ◽

2014 ◽

Vol 2014 ◽

pp. 1-7 ◽

Cited By ~ 29

Author(s):

Carlo Cervellati ◽

Arianna Romani ◽

Davide Seripa ◽

Eleonora Cremonini ◽

Cristina Bosi ◽

...

Keyword(s):

Oxidative Stress ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Late Onset ◽

Healthy Controls ◽

Prodromal Phase ◽

Systemic Oxidative Stress ◽

By Products

Mild cognitive impairment (MCI) is regarded as a prodromal phase of late onset Alzheimer’s disease (LOAD). It has been proposed that oxidative stress (OxS) might be implicated in the pathogenesis of LOAD. The aim of this study was to investigate whether a redox imbalance measured as serum level of hydroperoxides (i.e., by-products of lipid peroxidation) and/or serum antioxidant capacity might be predictive of the clinical progression of MCI to LOAD. The levels of these two markers were measured in 111 patients with MCI (follow-up:2.0 ± 0.6years), 105 patients with LOAD, and 118 nondemented healthy controls. Multivariate analysis adjusted for potential confounding factors, including age, gender, smoking, and comorbidities, showed a significant increase (P<0.05) in baseline levels of OxS in MCI and LOAD as compared to cognitive healthy controls. No differences in either of OxS markers were found by comparing MCI patients who converted (n = 29) or not converted (n = 82) to LOAD. Overall, these results suggest that systemic OxS might be a precocious feature of MCI and LOAD. However, the role of OxS as an early prognostic marker of progression to LOAD needs further investigations.

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Effect of DHT-Induced Hyperandrogenism on the Pro-Inflammatory Cytokines in a Rat Model of Polycystic Ovary Morphology

Medicina ◽

10.3390/medicina56030100 ◽

2020 ◽

Vol 56 (3) ◽

pp. 100

Author(s):

Abhaya Krishnan ◽

Sridhar Muthusami ◽

Loganayaki Periyasamy ◽

Jone A. Stanley ◽

Vasudevan Gopalakrishnan ◽

...

Keyword(s):

Inflammatory Markers ◽

Polycystic Ovary ◽

Elevated Serum ◽

Model System ◽

Reproductive Age ◽

Albino Rats ◽

Low Grade ◽

Tnf Α ◽

Inflammatory State

Background and Objectives: Polycystic ovary syndrome (PCOS) is one of the most prevalent disorders among women of reproductive age. It is considered as a pro-inflammatory state with chronic low-grade inflammation, one of the key factors contributing to the pathogenesis of this disorder. Polycystic ovary is a well-established criterion for PCOS. The present investigation aimed at finding the role of hyperandrogenism, the most important feature of PCOS, in the development of this inflammatory state. To address this problem, we adopted a model system that developed polycystic ovary morphology (PCOM), which could be most effectively used in order to study the role of non-aromatizable androgen in inflammation in PCOS. Materials and Methods: Six rats were used to induce PCOM in 21-days-old female Wistar albino rats by using a pre-determined release of dihydrotestosterone (DHT), a potent non-aromatizable androgen, achieved by implanting a DHT osmotic pump, which is designed to release a daily dose of 83 μg. Results: After 90 days, the rats displayed irregular estrous cycles and multiple ovarian cysts similar to human PCOS. Elevated serum inflammatory markers such as tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), and the presence of a necrotic lesion in the liver, osteoclast in the femur, multinucleated giant cells and lymphocytes in the ovary based on histopathological observation of DHT-treated rats clearly indicated the onset of inflammation in the hyperandrogenic state. Our results show no significant alterations in serum hormones such as luteinizing hormone (LH), follicle stimulating hormone (FSH), insulin, and cortisol between control and hyperandrogenised rats. DHT was significantly elevated as compared to control. mRNA studies showed an increased expression level of TNF-α and IL-1β, further, the mRNA expression of urocortin 1 (Ucn-1) was stupendously elevated in the liver of hyperandrogenised rats. Conclusions: Thus, results from this study provide: (1) a good PCOM model system in order to study the inflammatory changes in PCOS aspects, (2) alteration of inflammatory markers in PCOM rats that could be either due to its direct effect or by the regulation of various inflammatory genes and markers in the liver of hyperandrogenic state suggesting the regulatory role of DHT, and (3) alteration in stress-related protein in the liver of PCOM rats.

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Hyperandrogenism, Insulin Resistance, and Acanthosis Nigricans (HAIR-AN) Syndrome Reflects Adipose Tissue Dysfunction (“Adiposopathy” or “Sick Fat”) in Asian Indian Girls

Dermatology ◽

10.1159/000512918 ◽

2021 ◽

pp. 1-9

Author(s):

Kritika Agrawal ◽

Rachita Mathur ◽

Naincy Purwar ◽

Sandeep Kumar Mathur ◽

Deepak Kumar Mathur

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

Inflammatory Markers ◽

Tertiary Care ◽

Serum Adiponectin ◽

Primary Role ◽

Care Hospital ◽

Adipose Tissue Dysfunction ◽

Tnf Α

Background: Whether HAIR-AN syndrome and polycystic ovarian syndrome (PCOS) are distinct entities or represent a phenotypic spectrum of the same syndrome is still unclear. HAIR-AN syndrome is characterized by high insulin resistance, obesity, and hyperinsulinemia as compared to PCOS and could represent adipose tissue dysfunction as the primary pathophysiologic trigger. This study was undertaken to study the role of adipose tissue dysfunction in HAIR-AN syndrome and PCOS using adipocytokines as surrogate markers of “adiposopathy.” Materials and Methods: A cross-sectional observational study was conducted at a tertiary care hospital over a period of 1 year. Serum adiponectin, leptin, IL-6, and TNF-α levels were measured in 30 women with HAIR-AN syndrome and in 30 women with PCOS. Correlations between adipocytokines, inflammatory markers, serum testosterone, and serum insulin were determined. Data analysis was performed using the SPSS version 23.0 (IBM SPSS Statistics Inc., Chicago, IL, USA) software program. Results: Women with HAIR-AN syndrome had significantly higher hyperandrogenemia, hyperinsulinemia, and insulin resistance as compared to PCOS women. They also had high leptin levels and lower adiponectin levels (p < 0.001). However, the levels of inflammatory markers (TNF-α and IL-6) were similar in both the groups (p > 0.05). Serum adiponectin showed a negative correlation with HOMA-IR and testosterone levels, while leptin showed a positive correlation with both in HAIR-AN patients while no such correlation was found in the PCOS group. Conclusion: The significantly raised adipocytokines in HAIR-AN syndrome patients as compared to PCOS patients indicates the primary role of adipose tissue dysfunction (“adiposopathy”) in the pathogenesis of HAIR-AN syndrome while only a minor role, if any, in PCOS. Both these syndromes stand as distinct entities pathogenically with an overlapping phenotype.

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Study of serum traditional and nontraditional biomarkers in Rheumatoid arthritis patients

International Journal of Research in Pharmaceutical Sciences ◽

10.26452/ijrps.v11i4.3966 ◽

2020 ◽

Vol 11 (4) ◽

pp. 7585-7592

Author(s):

Vinod A N ◽

Leena Chand ◽

Preeti R Y ◽

Harshitha S ◽

Prahaladh R

Keyword(s):

Rheumatoid Arthritis ◽

Inflammatory Markers ◽

Cartilage Oligomeric Matrix Protein ◽

Matrix Protein ◽

Cross Sectional Study ◽

Healthy Controls ◽

Sectional Study ◽

Cross Sectional ◽

Significant Difference

The study of biomarkers in Rheumatoid arthritis (RA) is highly indispensable to understand mechanisms of pathogenesis, diagnosis, prognosis, and treatment of disease. The role of traditional biomarkers like Anti-CCP, RF, and inflammatory markers like ESR and CRP is well established. In this study, we aimed to measure nontraditional biomarkers like Hyaluronic acid (HA), Cartilage oligomeric matrix protein (COMP), and Osteocalcin in the serum of RA patients and also to establish an association with traditional markers. It was a cross-sectional study involving 152 RA patients based on the 1987 ACR criteria for the diagnosis of RA and 68 age‑ and sex-matched healthy controls. After the clinical examination, traditional markers were assessed to measure the disease activity along with non traditional markers in RA patients. All the values were expressed as median (25th–75th percentile). In our study, there was a significant increase in serum HA levels in RA patients compared to healthy controls (p < 0.03), whereas no significant difference in serum COMP and osteocalcin levels. The traditional inflammatory markers were significantly increased in RA patients than controls with (p < 0.001). The serum HA levels were significantly correlated with traditional markers in RA patients. Conclusion: Significant increase in serum HA level in RA patients indicating synovial inflammation, but there were no notable changes in COMP and osteocalcin level in serum presuming the combination of these markers may be useful along with traditional markers in the different stages of RA.

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