Oral administration of Weissella and Pediococcus sp alleviates formalin induced inflammation in rats by Cytokine Modulation

This study was designed to study the cytokine modulatory activity of three lactic acid bacteria (LAB) strains, Weisella cibaria II-1-59, Weisella confusa JMC 1093, and Pediococcus pentosaceus DSM20336 isolated from a Nigerian locally fermented food condiment; “iru” using paw oedema acute inflammatory model induced with 1% formalin in Wistar rats. Rats were distributed into six groups (A-F). Rats in Groups A were neither administered formalin nor treated with LAB, while Group B received formalin injection only. Rats in Groups C, D, and E were administered formalin and were treated orally with 2 × 107 CFU/ml of Weisella cibaria II-1-59, Weisella confusa JMC 1093, and Pediococcus pentosaceus DSM20336 respectively, while Group F received diclofenac sodium treatment following administration of formalin. The dose of LAB strain used for the oral treatment was 2 × 107 CFU/ml for all the groups while the dose of diclofenac sodium used was 150 mg/kg body weight of the rats. Paw thickness (mm) was checked at t = 0, 1, 4, 8, 24, 72, 168 and 336 h. Cytokine assay for C-reactive protein (CRP), Interleukin (IL-10) and Transforming growth factor (TGF-β) was performed on serum samples of the rats using Enzyme-linked immunosorbent assay (ELISA). Oral administration of W. cibaria II-1-59 showed the best significant decrease in the paw thickness of the rats, which was followed by P. pentosaceus DSM20336 and W. confusa JMC 1093 respectively, and was shown to be statistically significant at P<0.05. There was also a significant decrease (below standard 2000 pg/ml) in the secretion of pro-inflammatory biomarker (CRP) in all LAB treated groups at 1 hour, while there was an increase in the serum levels of anti-inflammatory cytokines IL-10 and TGF- β in Groups C-E rats which was maximally increased in W. confusa JMC 1093 treated rats. This study suggests that W. cibaria II-1-59, W. confusa JMC 1093 and P. pentosaceus DSM20336 possess anti-inflammatory potentials. Keywords: Inflammation, Cytokines, Weisella, Formalin, Oedema, Pediococcus

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miR-128-3p inhibits apoptosis and inflammation in LPS-induced sepsis by targeting TGFBR2

Open Medicine ◽

10.1515/med-2021-0222 ◽

2021 ◽

Vol 16 (1) ◽

pp. 274-283

Author(s):

Peng Yang ◽

Jianhua Han ◽

Shigeng Li ◽

Shaoning Luo ◽

Xusheng Tu ◽

...

Keyword(s):

Transforming Growth Factor Beta ◽

Transforming Growth Factor ◽

Quantitative Polymerase Chain Reaction ◽

Luciferase Reporter ◽

Enzyme Linked Immunosorbent Assay ◽

Serum Samples ◽

Aberrant Expression ◽

Protein Levels ◽

Apoptosis And Inflammation ◽

Hk2 Cells

Abstract Background Sepsis is a systemic inflammatory response that can lead to the dysfunction of many organs. The aberrant expression of miRNAs is associated with the pathogenesis of sepsis. However, the biological functions of miR-128-3p in sepsis remain largely unknown, and its mechanism should be further investigated. This study aimed to determine the regulatory network of miR-128-3p and TGFBR2 in lipopolysaccharide (LPS)-induced sepsis. Methods The expression levels of miR-128-3p and transforming growth factor beta receptors II (TGFBR2) were detected by quantitative polymerase chain reaction (qPCR). The protein levels of TGFBR2, Bcl-2, Bax, cleaved caspase 3, Smad2, and Smad3 were measured by western blot. Cell apoptosis was analyzed by flow cytometry. Cytokine production was detected by enzyme-linked immunosorbent assay (ELISA). The binding sites of miR-128-3p and TGFBR2 were predicted by Targetscan online software and confirmed by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Results The level of miR-128-3p was decreased, and TGFBR2 expression was increased in serum samples of sepsis patients and LPS-induced HK2 cells. Overexpression of miR-128-3p or knockdown of TGFBR2 ameliorated LPS-induced inflammation and apoptosis. Moreover, TGFBR2 was a direct target of miR-128-3p, and its overexpression reversed the inhibitory effects of miR-128-3p overexpression on inflammation and apoptosis in LPS-induced HK2 cells. Besides, overexpression of miR-128-3p downregulated TGFBR2 to suppress the activation of the Smad signaling pathway. Conclusion miR-128-3p could inhibit apoptosis and inflammation by targeting TGFBR2 in LPS-induced HK2 cells, which might provide therapeutic strategy for the treatment of sepsis.

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13 Lipocalin 2 exerts protective activity by alleviating inflammatory responses

Journal of Animal Science ◽

10.1093/jas/skz258.035 ◽

2019 ◽

Vol 97 (Supplement_3) ◽

pp. 17-19

Author(s):

Shuhui Li

Keyword(s):

Inflammatory Cytokines ◽

Protective Factor ◽

Transforming Growth Factor ◽

Inflammatory Responses ◽

Enzyme Linked Immunosorbent Assay ◽

Lipocalin 2 ◽

Continuous Increase ◽

Raw264.7 Macrophages ◽

Arginase 1 ◽

Anti Inflammatory

Abstract Lipocalin 2 (Lcn2) is an essential component of the innate immune system and exerts significant immunomodulatory effects in vitro. The aim of current study was to investigate the expression profile of Lcn2 during inflammatory process and explore the role of Lcn2 in the anti-inflammatory responses. Western blot, real-time quantitative PCR, immunofluorescence (IF) and enzyme-linked immunosorbent assay (ELISA) were employed. Firstly, we evaluated the temporospatial expression of Lcn2 of mice after inflammatory stimuli by lipopolysaccharides (LPS). In vivo, LPS induced both mRNA and protein levels of Lcn2 significantly (P < 0.01) in liver, jejunum and ileum. Lcn2 exhibited a continuous increase by 8 h and peaked by 24 h post challenges. Secondly, we challenged Lcn2-deficient (Lcn2-/-) mice and wild-type (WT) mice with peripheral LPS and determined effects on inflammation. In contrast to WT mice, Lcn2-/- mice showed distinct inflammatory injury in liver, jejunum, ileum and spleen with significantly elevated pro-inflammatory cytokines interleukin-6 (IL-6) and interleukin-1b (IL-1b) and decreased anti-inflammatory cytokine interleukin-10 (IL-10). Thirdly, we isolated bone marrow-derived macrophages (BMDM) from Lcn2-/- mice and WT mice to evaluate their functions. After LPS challenge, Lcn2-/- BMDM showed aggravated inflammatory reaction as pro-inflammatory factors tumour necrosis factor-α (TNF-α), IL-6, IL-1b and inducible nitric oxide synthase (iNOS) increased (P < 0.05) while anti-inflammatory cytokines IL-10, transforming growth factor β1 (TGF-β1) and arginase-1(Arg-1) decreased significantly (P < 0.05) compared with WT BMDM. This phenomenon could be relieved when adding recombinant Lcn2 (P < 0.05). The exogenous addition of Lcn2 on mice RAW264.7 macrophages stimulated by LPS also conformed this point. These findings demonstrated that Lcn2 served as a potent protective factor in response to systemic inflammation, and elevated Lcn2 expression during inflammatory conditions was presumed to play an effective role in alleviating inflammatory responses.

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The Effects of New Zealand Grown Ginseng Fractions on Cytokine Production from Human Monocytic THP-1 Cells

Molecules ◽

10.3390/molecules26041158 ◽

2021 ◽

Vol 26 (4) ◽

pp. 1158

Author(s):

Wei Chen ◽

Prabhu Balan ◽

David G. Popovich

Keyword(s):

New Zealand ◽

Inflammatory Cytokines ◽

Transforming Growth Factor Beta ◽

Inflammatory Cytokine ◽

Transforming Growth Factor ◽

Enzyme Linked Immunosorbent Assay ◽

High Dose ◽

Tnf Α ◽

Anti Inflammatory ◽

Pro Inflammatory Cytokines

Pro-inflammatory cytokines and anti-inflammatory cytokines are important mediators that regulate the inflammatory response in inflammation-related diseases. The aim of this study is to evaluate different New Zealand (NZ)-grown ginseng fractions on the productions of pro-inflammatory and anti-inflammatory cytokines in human monocytic THP-1 cells. Four NZ-grown ginseng fractions, including total ginseng extract (TGE), non-ginsenoside fraction extract (NGE), high-polar ginsenoside fraction extract (HPG), and less-polar ginsenoside fraction extract (LPG), were prepared and the ginsenoside compositions of extracts were analyzed by HPLC using 19 ginsenoside reference standards. The THP-1 cells were pre-treated with different concentrations of TGE, NGE, HPG, and LPG, and were then stimulated with lipopolysaccharide (LPS). The levels of pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), and anti-inflammatory cytokines, such as interleukin-10 (IL-10), and transforming growth factor beta-1 (TGF-β1), were determined by enzyme-linked immunosorbent assay (ELISA). TGE at 400 µg/mL significantly inhibited LPS-induced TNF-α and IL-6 productions. NGE did not show any effects on inflammatory secretion except inhibited IL-6 production at a high dose. Furthermore, LPG displayed a stronger effect than HPG on inhibiting pro-inflammatory cytokine (TNF-α, IL-1β, and IL-6) productions. Particularly, 100 µg/mL LPG not only significantly inhibited the production of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6, but also remarkably enhanced the production of anti-inflammatory cytokine IL-10. NZ-grown ginseng exhibited anti-inflammatory effects in vitro, which is mainly attributed to ginsenoside fractions (particularly less-polar ginsenosides) rather than non-saponin fractions.

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Effect of Chondroitin Sulfate on Blood Serum Cytokine Profile during Carrageenan-induced Edema and Monoiodoacetate-induced Osteoarthritis in Rats

Reviews on Recent Clinical Trials ◽

10.2174/1574887113666181102111247 ◽

2019 ◽

Vol 14 (1) ◽

pp. 50-55 ◽

Cited By ~ 5

Author(s):

Oleksandr Korotkyi ◽

Andrii Vovk ◽

Oksana Blokhina ◽

Kateryna Dvorshchenko ◽

Tetyana Falalyeyeva ◽

...

Keyword(s):

Knee Joint ◽

Blood Serum ◽

Chondroitin Sulfate ◽

Transforming Growth Factor ◽

Experimental Models ◽

Cytokine Profile ◽

Enzyme Linked Immunosorbent Assay ◽

Blood Cytokines ◽

Anti Inflammatory ◽

Therapeutic Administration

Background: Blood cytokines affect the development of inflammatory processes in both normal and pathological states. We have studied changes in the concentration of interleukins (ILs) - 1β, IL-4, IL-10, IL-12B p40, transforming growth factor β (TGF β), tumor necrosis factor (TNF-α) in acute carrageenan-induced inflammation and degenerative-dystrophic changes of knee joint caused by monoiodoacetate-induced Osteoarthritis (OA) in experimental models on rats. We also investigated the change in the cytokine profile during prophylactic and therapeutic administration of chondroitin sulfate to animals under experimental conditions. </P><P> Methods: The concentration of the cytokines was measured in blood serum by enzyme-linked immunosorbent assay. Results: The manifestation of articular lesions was characterized by a disturbance in the balance between proinflammatory (IL-1β, IL-12B p40, TNF-α) and anti-inflammatory (IL-4, IL-10, TGF -β) cytokines. Conclusion: A reduction in the concentration of proinflammatory cytokines in blood serum after prophylactic and therapeutic administration of chondroitin sulfate to the rat with experimental models of acute inflammation of the hind limb and degenerative-dystrophic changes in the knee joint with OA is associated with anti-inflammatory and regenerative properties of the drug.

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Anti-Inflammatory Interleukin 10 Inversely Relates to Coronary Atherosclerosis in Persons With Human Immunodeficiency Virus

The Journal of Infectious Diseases ◽

10.1093/infdis/jiz254 ◽

2019 ◽

Vol 221 (4) ◽

pp. 510-515 ◽

Cited By ~ 1

Author(s):

Lindsay T Fourman ◽

Charles F Saylor ◽

Lediya Cheru ◽

Kathleen Fitch ◽

Sara Looby ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Coronary Atherosclerosis ◽

Fold Increase ◽

Coronary Plaque ◽

Interleukin 10 ◽

Computed Tomographic Angiography ◽

Enzyme Linked Immunosorbent Assay ◽

Serum Samples ◽

Immunodeficiency Virus ◽

Anti Inflammatory

Abstract Interleukin 10 (IL-10) is an anti-inflammatory cytokine that may be protective against coronary atherosclerosis. In an observational study of persons with human immunodeficiency virus (PWH) and uninfected controls, IL-10 was measured in serum samples by means of enzyme-linked immunosorbent assay, and coronary atherosclerosis was assessed using computed tomographic angiography. Among PWH, a 10-fold decrease in IL-10 was associated with a 2.6-fold increase in the odds of coronary plaque (P = .01), after controlling for traditional and nontraditional cardiovascular risk factors. IL-10 was also inversely associated with total coronary plaque (ρ = −0.19; P = .02) and noncalcified coronary plaque (ρ = −0.24; P = .004). Our findings suggest a role for IL-10 in mitigating atherosclerosis in PWH. Clinical Trials Registration. NCT00455793

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The novel role of IL-37 to enhance the anti-inflammatory response of regulatory T cells in patients with peripheral atherosclerosis

Vascular ◽

10.1177/1708538120921735 ◽

2020 ◽

Vol 28 (5) ◽

pp. 629-642 ◽

Cited By ~ 1

Author(s):

Hassan Lotfy ◽

Marwa Moaaz ◽

Mai Moaaz

Keyword(s):

T Cells ◽

Regulatory T Cells ◽

Inflammatory Response ◽

Transforming Growth Factor Beta ◽

Lower Limb ◽

Transforming Growth Factor ◽

Severe Disease ◽

Cytokine Secretion ◽

Enzyme Linked Immunosorbent Assay ◽

Anti Inflammatory

Objectives Regulatory T cells (Tregs) mediate immunomodulation and protect against atherosclerosis. It is considered that reducing the amount of pro-inflammatory mediators could be achieved by enhancing the anti-inflammatory response, and this may be considered one of the main targets for therapy development. The inhibitory cytokines secreted by Tregs mainly include interleukin-10 (IL-10) and transforming growth factor-beta (TGF-β). Based on its known immunosuppressive involvement with other inflammatory disorders, we hypothesized that the newly characterized cytokine interleukin-37 (IL-37) might be associated with the inhibitory functions of Treg in atherosclerosis. Immune regulatory functions of IL-37 have not been completely clarified. Accordingly, we speculated that IL-37 might play a regulatory role in the immunosuppression of Tregs in atherosclerotic disease. Methods Real-time polymerase chain reaction and enzyme linked immunosorbent assay were used to test gene expression and protein levels of IL-37 in peripheral blood and localized freshly resected arterial tissues from 84 patients with peripheral arterial occlusive disease and 50 non-atherosclerotic subjects. Results were correlated to disease hallmarks. We also evaluated the ability of recombinant IL-37 to modulate Treg cytokine secretion and T cell inhibition in relation to atherosclerotic disorder in vitro. Results: Our results revealed that IL-37 was increased in patients with chronic lower limb atherosclerotic ischemia, compared to non-atherosclerotic controls. In addition, the expression levels of circulating IL-37 correlated with disease severity of chronic lower limb ischemia. Supplementation with rIL-37 augmented levels of released IL-10 and TGF-β in supernatants of T cells co-cultured with Tregs in the enrolled patients. Conclusions: Results suggest a role for IL-37 in mediating anti-inflammatory functions in the atherosclerotic process, potentially involving enhancement of Treg inhibitory function and anti-inflammatory cytokine secretion with a particularly marked direct response in severe disease.

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Efficacy of Lychnopholide Polymeric Nanocapsules after Oral and Intravenous Administration in Murine Experimental Chagas Disease

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00178-16 ◽

2016 ◽

Vol 60 (9) ◽

pp. 5215-5222 ◽

Cited By ~ 13

Author(s):

Carlos Geraldo Campos de Mello ◽

Renata Tupinambá Branquinho ◽

Maykon Tavares Oliveira ◽

Matheus Marques Milagre ◽

Dênia Antunes Saúde-Guimarães ◽

...

Keyword(s):

Oral Administration ◽

Chagas Disease ◽

Intravenous Administration ◽

Oral Treatment ◽

Chronic Phase ◽

Enzyme Linked Immunosorbent Assay ◽

Chronic Infections ◽

Content Type ◽

Polymeric Nanocapsules ◽

Cure Rates

ABSTRACTThe etiological treatment of Chagas disease remains neglected. The compounds available show several limitations, mainly during the chronic phase. Lychnopholide encapsulated in polymeric nanocapsules (LYC-NC) was efficacious in mice infected withTrypanosoma cruziand treated by intravenous administration during the acute phase (AP). As the oral route is preferred for treatment of chronic infections, such as Chagas disease, this study evaluated the use of oral LYC-NC in the AP and also compared it with LYC-NC administered to mice by the oral and intravenous routes during the chronic phase (CP). The therapeutic efficacy was evaluated by fresh blood examination, hemoculture, PCR, and enzyme-linked immunosorbent assay (ELISA). The cure rates in the AP and CP were 62.5% and 55.6%, respectively, upon oral administration of LYC–poly(d,l-lactide)–polyethylene glycol nanocapsules (LYC-PLA-PEG-NC) and 57.0% and 30.0%, respectively, with LYC–poly-ε-caprolactone nanocapsules (LYC-PCL-NC). These cure rates were significantly higher than that of free LYC, which did not cure any animals. LYC-NC formulations administered orally during the AP showed cure rates similar to that of benznidazole, but only LYC-NC cured mice in the CP. Similar results were achieved with intravenous treatment during the CP. The higher cure rates obtained with LYC loaded in PLA-PEG-NC may be due to the smaller particle size of these NC and the presence of PEG, which influence tissue diffusion and the controlled release of LYC. Furthermore, PLA-PEG-NC may improve the stability of the drug in the gastrointestinal tract. This work is the first report of cure of experimental Chagas disease via oral administration during the CP. These findings represent a new and important perspective for oral treatment of Chagas disease.

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Anti-Inflammatory Activity of Marine Sponge Aaptos sp. to the Plasma Interleukin-1β Level in Wistar Male Rats

Pharmacology and Clinical Pharmacy Research ◽

10.15416/pcpr.v4i2.24269 ◽

2019 ◽

Vol 4 (2) ◽

pp. 35

Author(s):

Adryan Fristiyohadi ◽

Wahyuni Wahyuni ◽

Wa OIL. Kalimin ◽

La OMJ. Permana ◽

Saripuddin Saripuddin ◽

...

Keyword(s):

Diclofenac Sodium ◽

Ethanolic Extract ◽

Negative Control ◽

The Body ◽

Inflammatory Activity ◽

Male Rats ◽

Enzyme Linked Immunosorbent Assay ◽

Significant Difference ◽

Anti Inflammatory ◽

Wistar Male Rats

Inflammation is the response of the body to injury and infection characterized by swelling, heat, pain, and redness. This study aimed to investigate the anti-inflammatory effect of Aaptos sp. ethanolic extract to plasma interleukin (IL)-1β level of Wistar male rats. Aaptos sp. was macerated with 96% ethanol for 3 x 24 hours. Inflammation was induced with administration of 1% carrageenan intraplantarly. Animals were divided into 5 treatment groups, i.e., positive control (diclofenac sodium 3598 ppm); Aaptos sp extract 50 ppm; Aaptos sp extract 100 ppm Aaptos sp extract 200 ppm; and negative control (0.5% Na CMC). After 1 hour, blood was collected and assayed using enzyme-linked immunosorbent assay (ELISA) kit. The results showed that plasma IL-1β levels of animals were decreased by Aaptos sp ethanolic extract. The administration of 50 ppm of extract showed no significant difference (p>0.05) in IL-1β level in first and second hour measurement, but indicated a statistically significant decrease after three hour (p<0.05). The administration of 100 ppm of extract showed no significant difference (p>0.05) in every hour. Significant reduction was observed in the administration of 200 ppm of extract, but the elevation of IL-1β levels was also observed at third hour measurement. In conclusion, ethanolic extract of Aaptos sp. had anti-inflammatory activity and its effective dose was 50 ppm.

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The Effects of Titanium Surfaces Modified with an Antimicrobial Peptide GL13K by Silanization on Polarization, Anti-Inflammatory, and Proinflammatory Properties of Macrophages

BioMed Research International ◽

10.1155/2020/2327034 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9

Author(s):

Xuxi Chen ◽

Lin Zhou ◽

Dong Wu ◽

Wenxiu Huang ◽

Yanjun Lin ◽

...

Keyword(s):

Antimicrobial Peptide ◽

Titanium Surface ◽

Transforming Growth Factor ◽

Interleukin 1 ◽

Enzyme Linked Immunosorbent Assay ◽

M2 Macrophages ◽

Term Survival ◽

M1 Macrophages ◽

Titanium Surfaces ◽

Anti Inflammatory

The polarization of macrophages and its anti-inflammatory and proinflammatory properties play a significant role in host response after implant placement to determine the outcome of osseointegration and long-term survival. In the previous study, we immobilized an antimicrobial peptide, GL13K, onto titanium surfaces to provide immune regulation property. In the herein presented study, we aimed at investigating whether GL13K immobilized titanium surface could improve osteogenesis and reduce the inflammatory reaction around the biomaterials by altering macrophage response. We evaluated the cell proliferation of the different phenotypes of macrophages seeded in GL13K-coated titanium surface, which indicated an inhibition of M1 macrophages and a good cytocompatibility to M2 macrophages. Then, we measured the inflammatory and anti-inflammatory activity of the M1 and M2 macrophages seeded on the GL13K-coated titanium surfaces. The results of the enzyme-linked immunosorbent assay and quantitative reverse transcription-polymerase chain reaction showed that the group with the GL13K modified surface had a downregulation in the expression level of the tumor necrosis factor-α and interleukin-1β in M1 macrophages and an upregulation of IL-10 and transforming growth factor-β3 (TGF-β3) levels in M2 macrophages. This study demonstrated that the GL13K modified titanium surfaces can regulate macrophages’ polarization and the expression of inflammatory and anti-inflammatory effects, reducing the effects of the inflammatory process, which may promote the process of bone regeneration and osseointegration.

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Rapid Communication: Plasma Interleukin-35 in Children with Autism

Brain Sciences ◽

10.3390/brainsci9070152 ◽

2019 ◽

Vol 9 (7) ◽

pp. 152 ◽

Cited By ~ 2

Author(s):

Destanie Rose ◽

Paul Ashwood

Keyword(s):

Transforming Growth Factor Beta ◽

Plasma Levels ◽

Transforming Growth Factor ◽

Autism Spectrum ◽

Enzyme Linked Immunosorbent Assay ◽

The Novel ◽

Typically Developing ◽

Aberrant Behavior Checklist ◽

Children With Asd ◽

Anti Inflammatory

In autism spectrum disorders (ASD) many individuals have co-morbid immune dysregulation that can lead to inflammation in the brain and periphery. The novel cytokine interleukin (IL)-35 has described anti-inflammatory properties; however, the plasma levels of IL-35 in children with ASD have never been investigated. The plasma levels of IL-35 were measured by an enzyme-linked immunosorbent assay in 30 children with ASD and 39 typically developing (TD) controls. In the current study, we found that plasma IL-35 levels were significantly decreased in children with ASD compared with TD children. Furthermore, lower IL-35 levels were associated with worse behaviors as assessed using the aberrant behavior checklist. These findings are in line with other observations of decreased regulatory cytokines such as transforming growth factor beta and IL-10 in ASD, and associations with severity of behaviors. In conclusion, regulating the expression of IL-35 may provide a new possible target for the treatment of immune issues in ASD to address an imbalance between pro- and anti-inflammatory signals that alter the behavioral phenotype.

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