Prevotella Induces the Production of Th17 Cells in the Colon of Mice

Th17-mediated mucosal inflammation is related to increased Prevotella bacterial abundance. The actual involvement of Prevotella in the development and accumulation of intestinal Th17 cells at a steady state, however, remains undefined. Herein, we investigated the role of Prevotella in inducing intestinal Th17 cells in mice. Mice were treated with a combination of broad-spectrum antibiotics (including ampicillin, neomycin sulfate, vancomycin hydrochloride, and metronidazole) in their drinking water for 4 weeks and then gavaged with Prevotella for 4 weeks. After inoculation, 16S rDNA sequencing was used to verify the colonization of Prevotella in the colon of mice. The IL-17A as well as IL-17A-expressing T cells was localized and quantified by an immunofluorescence assay (IFA) of colon sections. Th17 cells in the mesenteric lymph nodes of mice were counted by flow cytometry. Systemic immune response to Prevotella colonization was evaluated based on the serum levels of IL-6, TNF-α, IL-1β, IL-17A, IL-10, IL-4, IFN-γ, and IL-2. Th17-polarizing cytokines (IL-6, TNF-α, IL-1β, and IL-2) induced by Prevotella were evaluated by stimulation of bone marrow-derived dendritic cells (BMDCs). Results revealed that after inoculation, Prevotella successfully colonized the intestine of mice and induced the production and accumulation of colonic Th17 cells in the colon. Moreover, Prevotella elevated some of the Th17-related cytokines in the serum of mice. And Th17-polarizing cytokines (IL-6 and IL-1β) produced by BMDCs were mediated mainly through the interaction between Prevotella and Toll-like receptor 2 (TLR2). In conclusion, our data suggest that Prevotella induces the production of Th17 cells in the colon of mice, thus highlighting the potential role of Prevotella in training the intestinal immune system.

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CHANGES THE CYTOKINE PROFILE AND CALCIUM-REGULATING HORMONES IN RHEUMATOID ARTHRITIS

Russian Clinical Laboratory Diagnostics ◽

10.18821/0869-2084-2019-64-11-673-676 ◽

2019 ◽

Vol 64 (11) ◽

pp. 673-676

Author(s):

Asmaya Saftar Huseynova

Keyword(s):

Rheumatoid Arthritis ◽

Parathyroid Hormone ◽

Bone Loss ◽

Hypovitaminosis D ◽

Serum Levels ◽

Control Group ◽

Tnf Α ◽

High Production ◽

Serological Variant

The aim was to study the level of some cytokines (İL-2, İL-6, İL-8 TNFα) and calcium regulating hormones (calcitonin, parathyroid hormone, 25 (OH) D) in the blood of patients with rheumatoid arthritis (RA) depending on rheumatoid factor (RF) and the assessment of the role of the revealed violations in the pathogenesis of bone loss in this pathology. For this purpose, 74 patients with RA (59 women, 15 men) aged from 27 to 71 were examined. On the basis of RF in the blood serum, the patients were divided into 2 groups: seronegative and seropositive RA. The control group included 16 healthy individuals (13 women, 3 men). The results obtained that the serological variant of RA affects the serum levels of proinflammatory cytokines and calcium-regulating hormones: more pronounced changes were found in seropositive RA. The high production of IL-2, IL-6, IL-8, TNF-α and parathyroid hormone detected in both groups of patients undoubtedly contributes to the mechanisms of bone loss in RA. In both groups we detected hypovitaminosis D. This results recommended to use this vitamin in the complex treatment of RA.

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Serum Levels of IL-17, IL-6, TNF-α and Disease Activity in Patients with Rheumatoid Arthritis

Aktuelle Rheumatologie ◽

10.1055/s-0035-1564141 ◽

2016 ◽

Vol 42 (04) ◽

pp. 323-328 ◽

Cited By ~ 1

Author(s):

M. Beyazal ◽

G. Devrimsel ◽

M. Cüre ◽

A. Türkyılmaz ◽

E. Çapkın ◽

...

Keyword(s):

Disease Activity ◽

Severe Disease ◽

Serum Levels ◽

Necrosis Factor Alpha ◽

Tnf Α ◽

Factor Alpha ◽

High Level ◽

Necrosis Factor

Abstract Objective: The aim of this study was to evaluate serum levels of interleukin (IL)-17, IL-6, and tumor necrosis factor alpha (TNF-α) in RA patients and to assess the correlation of these cytokines with clinical and laboratory parameters. Materials and Methods: 48 patients with RA and 35 healthy volunteers were enrolled in the study. Disease activity was determined by disease activity score (DAS28) in patients with RA. Patients with RA were categorized as mild (DAS28≤3.2), moderate (3.2<DAS28≤5.1), and severe (5.1<DAS28) according to DAS28. The serum levels of IL-17, IL-6 and TNF-α cytokines were measured by enzyme-linked immuno sorbent assay. Results: The mean serum IL-17 and TNF-α levels did not differ between RA patients and controls (P>0.05). Serum IL-6 levels were significantly elevated in RA patients compared with controls (P<0.001). The increasing trend in mean serum IL-6 levels across group with mild, moderate, and severe disease activity was significant (P<0.001, respectively). In RA patients, serum IL-6 concentrations were significantly correlated with ESR, CRP, DAS28, and VAS (r=0.371, P=0.009; r=0.519, P<0.001; r=0.536, P<0.001; r=0.539, P<0.001, respectively). Also, Serum IL-17 concentrations demonstrated significant correlations with ESR, CRP, but not DAS28 (r=0.349, P=0.015; r=0.299, P=0.039; r=0.274, P=0.060, respectively). Serum TNF-α showed no significant correlation with disease activity indices. Conclusions: This study showed that patients with RA had significantly increased cytokine level for IL-6, but not IL-17 and TNF-α and high level of serum IL-6 cytokine was associated with disease activity. However, further follow-up studies involving large samples are required to clarify precise role of these cytokines in disease development and progress.

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IL-17A, IL-22, and IL-23 as Markers of Psoriasis Activity

Journal of Cutaneous Medicine and Surgery ◽

10.1177/1203475415584503 ◽

2015 ◽

Vol 19 (6) ◽

pp. 555-560 ◽

Cited By ~ 15

Author(s):

Christina Fotiadou ◽

Elizabeth Lazaridou ◽

Eleni Sotiriou ◽

Spiridon Gerou ◽

Athanasios Kyrgidis ◽

...

Keyword(s):

Th17 Cells ◽

Tumor Necrosis ◽

Serum Levels ◽

Sensitivity Analyses ◽

T Helper ◽

T Helper 1 ◽

Factor Α ◽

Necrosis Factor ◽

Active Disease

Introduction: T-helper 1 (Th1), Th17 cells, and their related cytokines are implicated in psoriasis pathogenesis although the contribution of each group of cytokines in psoriasis activity has not been fully clarified. Objectives: To investigate whether Th17-related cytokines are associated with psoriasis activity. Methods: The serum levels of interleukin (IL)-1β, 6, 8, 17Α, 22, 23, and tumor necrosis factor-α (TNFα) were measured with flow cytometry in 35 patients with plaque psoriasis (21 with stable and 14 with active disease) and in 20 healthy controls. Results: Interleukin-6, 8, 17A, 22, 23, and TNFα were significantly elevated in psoriasis patients compared with controls. In the sensitivity analyses, patients with active disease showed significantly increased levels of IL-17A, IL-23, and IL-22 as compared to the group of patients with stable psoriasis. Conclusions: Our study highlights a possible crucial role of IL-17A, IL-22, and IL-23 in the activity of psoriasis and the early stages of the disease.

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The role of lymphoid tissue in the attenuation of the postoperative ileus

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00161.2012 ◽

2013 ◽

Vol 304 (4) ◽

pp. G401-G412 ◽

Cited By ~ 5

Author(s):

A. Koscielny ◽

D. Engel ◽

J. Maurer ◽

S. Wehner ◽

C. Kurts ◽

...

Keyword(s):

Transit Time ◽

Colonic Transit ◽

Lymphoid Organs ◽

Wild Type ◽

Mesenteric Lymph Nodes ◽

Mesenteric Lymph ◽

Tnf Α ◽

Secondary Lymphoid Organs ◽

Fluorescent Dextran

Standardized intestinal manipulation (IM) leads to local bowel wall inflammation subsequently spreading over the entire gastrointestinal tract. Previously, we demonstrated that this so-called gastrointestinal field effect (FE) is immune-mediated. The aim of this study was to investigate the role of secondary lymphoid organs [mesenteric lymph nodes (MLN), gut-associated lymphoid tissue (GALT)] in IM-mediated FE by employing mice with deficient secondary lymphoid organs (aly/aly, MLN ex) or by administration of 2-amino-2-[2-(4-octylphenyl)ethyl]-1,3-propanediol (FTY720), an immunomodulating agent that inhibits emigration of lymphocytes out of lymphoid organs. Small bowel muscularis, and colonic muscularis from wild-type mice as control, from aly/aly mice, FTY720-treated mice (daily dose of 1.0 mg/kg mouse ip starting 3 days before surgical procedure), and wild-type mice that had undergone removal of mesenteric lymph nodes before IM (MLN ex mice) were obtained after selective IM of the jejunum or sham operation. FE was analyzed by measuring transit time of orally administered fluorescent dextran in the gastrointestinal tract [geometric center (GC) of fluorescent dextran], colonic transit time, infiltration of myeloperoxidase-positive cells, and circular smooth muscle contractility. Furthermore, mRNA levels of inflammatory cytokines [interleukin (IL)-6, tumor necrosis factor (TNF)-α, macrophage inflammatory protein (MIP)-1α] were determined by Taqman-PCR. We observed a significantly reduced upregulation of proinflammatory cytokines (IL-6, TNF-α, MIP-1α) in colonic muscularis of MLN ex mice, aly/aly mice, and FTY720-treated mice compared with wild-type mice. Contractility of circular muscularis strips of the colon but not the jejunum was significantly improved in aly/aly mice and FTY720-treated wild-type mice. Additionally, inflammation of the colon determined by the number of myeloperoxidase-positive cells and colonic transit time were significantly improved in aly/aly mice, FTY720-treated wild-type mice, and in MLN ex mice. In summary, lack of secondary lymphoid organs (MLN + GALT) in aly/aly mice or administration of FTY720 abrogated FE after IM as opposed to wild-type mice. These data demonstrate that secondary lymphoid organs are involved in the propagation of FE and postoperative ileus. FTY720 indirectly affects FE by inhibiting migration of activated T cells from the jejunum and adjacent secondary lymphoid organs to the colon. These findings support the crucial role of the adaptive immune system in FE, most likely by a sphyngosine 1-phosphate-dependent mechanism.

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Adiponectin deficiency does not affect development and progression of spontaneous colitis in IL-10 knockout mice

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.90593.2008 ◽

2009 ◽

Vol 296 (2) ◽

pp. G382-G387 ◽

Cited By ~ 15

Author(s):

Maria Pini ◽

Melissa E. Gove ◽

Raja Fayad ◽

Robert J. Cabay ◽

Giamila Fantuzzi

Keyword(s):

Colonic Tissue ◽

Mesenteric Lymph Nodes ◽

Amyloid A ◽

Mesenteric Lymph ◽

Tnf Α ◽

Ifn Γ ◽

Circulating Levels ◽

Similar Decrease

The goal of this study was to investigate the role of the adipokine adiponectin (APN) in development of spontaneous colitis in IL-10 knockout (KO) mice. To this aim, we generated double IL-10 APN KO mice and compared their disease development to that of single IL-10 KO mice. Both IL-10 KO and double IL-10 APN KO mice spontaneously developed colitis of comparable severity. No significant differences in inflammatory infiltrate or crypt elongation were observed in colonic tissue obtained from IL-10 KO and double IL-10 APN KO mice at either 12 or 20 wk of age. A comparable increase in circulating levels of serum amyloid A and IFN-γ was observed in IL-10 KO and double IL-10 APN KO mice as disease progressed. In vitro stimulation of lymphocytes from mesenteric lymph nodes with anti-CD3 and anti-CD28 induced a significantly higher production of IL-17 and TNF-α in IL-10 KO and double IL-10 APN KO mice compared with their healthy littermates. No significant differences in cytokine production from lymphocytes or colonic mRNA expression of cytokines were observed between IL-10 KO and double IL-10 APN KO mice. Both IL-10 KO and double IL-10 APN KO mice had a similar decrease in body weight and bone mass compared with their respective healthy littermates. Finally, APN deficiency did not lead to development of insulin resistance, either in APN KO or double IL-10 APN KO mice. In conclusion, lack of APN does not play a significant role in the pathogenesis of spontaneous colonic inflammation in the IL-10 KO model.

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Genetic variants of interferon-gamma and its mRNA expression and inflammatory parameters in the pathogenesis of vitiligo

Biochemistry and Cell Biology ◽

10.1139/bcb-2016-0228 ◽

2017 ◽

Vol 95 (4) ◽

pp. 474-481 ◽

Cited By ~ 7

Author(s):

Rehab A. Karam ◽

Haidy E. Zidan ◽

Mohamed H. Khater

Keyword(s):

Elevated Serum ◽

Serum Levels ◽

Intercellular Adhesion Molecule ◽

Control Group ◽

Intercellular Adhesion Molecule 1 ◽

Inflammatory Parameters ◽

Increased Risk ◽

Tnf Α ◽

Ifn Γ

Although genetics plays an essential role in the pathogenesis of vitiligo, vitiligo pathogenesis is still unclear. Our aim was to investigate the role of IFN-γ expression and polymorphism in vitiligo susceptibility and whether intercellular adhesion molecule-1 (ICAM-1), tumor necrosis factor (TNF)-α, and TNF-β play a role in vitiligo pathogenesis as important inflammatory parameters. Eighty-five patients with vitiligo and 90 controls were investigated for IFN-γ gene expression by quantitative real-time PCR and genotyped for IFN-γ +874T/A (rs2430561) and IFN-γ +2109A/G (rs1861494) gene polymorphisms by sequence-specific primer (SSP)-PCR and PCR-restriction fragment length polymorphism (RFLP), respectively. Serum levels of inflammatory parameters were measured using ELISA. Frequencies of the +874 TT genotype and T allele were significantly higher in patients with active vitiligo than in stable patients (P = 0.01 and 0.03, respectively). Calculation of odds ratio suggested a 1.7-fold increased risk of vitiligo in individuals having the TA haplotype. We observed overexpression of IFN-γ mRNA with elevated serum levels of IFN-γ, ICAM-1, TNF-α, and TNF-β in patients with vitiligo when compared with the control group (P = 0.001, for all). In addition, these levels were elevated in patients with active vitiligo compared with stable patients with vitiligo (P = 0.008, 0.006, 0.01, 0.01, and 0.03, respectively), which suggests the involvement of these cytokines in disease activity. In conclusion, IFN-γ is a promising immunological marker in vitiligo pathogenesis.

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The role of IL-18 in addition to Th17 cytokines in rheumatoid arthritis development and treatment in women

Scientific Reports ◽

10.1038/s41598-021-94841-x ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Georgi Vasilev ◽

Irena Manolova ◽

Mariana Ivanova ◽

Iskren Stanilov ◽

Lyuba Miteva ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Disease Duration ◽

Early Stage ◽

Serum Levels ◽

Treatment Regimens ◽

Rheumatoid Arthritis Development ◽

Tnf Α ◽

Th17 Cytokines ◽

Pro Inflammatory Cytokines

AbstractWe aimed to analyze serum pro-inflammatory profiles of female rheumatoid arthritis (RA) patients and compare them with healthy women to establish the relative importance of pro-inflammatory cytokines in RA and their relation with different treatment regimens. Levels of six cytokines were determined by ELISA assays. A supervised dimensionality reducing approach (PLS-DA Analysis) was applied. All of the cytokines assayed were significantly elevated in the sera of RA female patients than healthy controls with fold change: 21-fold for IL-6; 6.1-fold for IL-17A; 2.5-fold for IL-23; 2.3-fold for IL-18; 1.94-fold for TNF-α; 1.7-fold for IL-12p40. According to the results of the PLS-DA analysis, IL-17A, IL-18, and TNF-α were of higher importance rank compared to IL-23 and IL-12p40. Women in the early stage of RA displayed significantly elevated IL-17A levels than those with longer disease duration: 8.04 pg/ml [8.04–175.3] vs 4.64 pg/ml [2.95–13.31], p = 0.007. IL-6 serum levels were related to higher disease activity. We have demonstrated altered cytokine production within female RA patients on different treatment regimens. Those on Tocilizumab therapy showed elevated IL-6 levels and decreased IL-17A versus the rest of the patients’ subgroups. In conclusion, our data support the pivotal role of IL-18 in addition to IL-6, IL-17A, and TNF-α as the hierarchical cytokines in the pathogenesis of RA, particularly valid for women. Therapy with biological agents targeting IL-18 in addition to the Th17 axis may be an adequate approach in RA patients.

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Different Cytokine Profiles in Children with Acute Appendicitis and Acute Mesenteric Lymphadenitis / Atðíirîga Citokînu Grupas Seruma Iekaisuma Mediatoru Izpausme Akûta Apendicîta Un Akûta Mezenteriâla Limfadenîta Gadîjumâ Bçrniem

Proceedings of the Latvian Academy of Sciences Section B Natural Exact and Applied Sciences ◽

10.1515/prolas-2015-0044 ◽

2015 ◽

Vol 69 (6) ◽

pp. 283-289

Author(s):

Astra Zviedre ◽

Arnis Eòìelis ◽

Pçteris Tretjakovs ◽

Antra Jurka ◽

Irisa Zîle ◽

...

Keyword(s):

Acute Appendicitis ◽

Surgical Intervention ◽

Serum Levels ◽

Mesenteric Lymphadenitis ◽

Surgical Disease ◽

Serum Cytokines ◽

Tnf Α ◽

Significant Difference ◽

Wilks Lambda

Abstract The aim of this study was to investigate the role of serum cytokines in the diagnosis of acute appendicitis (AA) and acute mesenteric lymphadenitis (AML). Data were collected prospectively on 7 to 18 year old children (October 2010 - October 2013): 31 patients with AA, 26 patients with AML, and 17 patients with elective non-inflammatory surgical disease were selected as controls. Serum levels of IL-10, IL-12(p70), IL-1β, IL-4, IL-6, IL-8, IL-17, MCP-1, EGF, TNF-α were measured. Patients with AA had significantly increased serum levels of IL-6(1) (z = -3.72; p = 0.0002) and IL-10(1) (z = -2.81; p = 0.005) compared to AML before any treatment. The consecutive measurements of MCP-1 in serum demonstrated a significant difference within 72 hours in the AA group (Wilks’ Lambda test 0.80; F(2;29) = 3.5; p = 0.04) and also in the AML group (Wilks’ Lambda test 0.70; F(2;24) = 5.0; p = 0.01). The increased values of IL-6 and IL-10 were the most reliable cytokines one hour before surgical intervention for patients with AA. MCP-1 values changed significantly within 72 hours after patient hospitalisation but did not differ between the groups, and could not be a helpful serum biomarker in distinguishing patients with AA and AML.

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Protective Effects of the Third Generation Vasodilatory Βeta - Blocker Nebivolol against D-Galactosamine - Induced Hepatorenal Syndrome in Rats

Open Access Macedonian Journal of Medical Sciences ◽

10.3889/oamjms.2017.173 ◽

2017 ◽

Vol 5 (7) ◽

pp. 880-892 ◽

Cited By ~ 1

Author(s):

Ahmed Atwa ◽

Rehab Hegazy ◽

Rania Mohsen ◽

Neamat Yassin ◽

Sanaa Kenawy

Keyword(s):

Hepatorenal Syndrome ◽

Histopathological Examination ◽

Serum Levels ◽

Heme Oxygenase 1 ◽

Protective Effects ◽

Necrosis Factor Alpha ◽

Tnf Α ◽

Advanced Liver Cirrhosis ◽

Factor Alpha

BACKGROUND: Renal dysfunction is very common in patients with advanced liver cirrhosis and portal hypertension. The development of renal failure in the absence of clinical, anatomical or pathological causes renal of failure is termed hepatorenal syndrome (HRS).AIM: The present study was constructed to investigate the possible protective effects of nebivolol (Nebi) against D-galactosamine (Gal)-induced HRS in rats.MATERIAL AND METHODS: Rats were treated with Nebi for ten successive days. On the 8th day of the experiment, they received a single dose of Gal. Serum levels of Cr, BUN, Na+ and K+ as well as AST, ALT, total bilirubin (TB), NH3 and endothelin-1 (ET-1) were determined following Gal administration. Moreover, renal and liver contents of MDA, GSH, F2-isoprostanes (F2-IPs), tumor necrosis factor-alpha (TNF-α), nuclear factor kappa-B (NF-кB), total nitric oxide (NO), in addition to activities of caspase-3 (Cas-3), heme oxygenase-1 (HO-1), inducible and endothelial NO synthase (iNOS and eNOS) enzymes were also assessed. Finally, histopathological examination was performed.RESULTS: Nebi attenuated Gal-induced renal and hepatic dysfunction. It also decreased the Gal-induced oxidative stress and inflammatory recruitment.CONCLUSION: Results demonstrated both nephroprotective and hepatoprotective effects of Nebi against HRS and suggested a role of its antioxidant, anti-inflammatory, anti-apoptotic and NO-releasing properties.

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