Effect of Atmospheric PM2.5 on Expression Levels of NF-κB Genes and Inflammatory Cytokines Regulated by NF-κB in Human Macrophage

Background Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with marked variation in its clinical presentation. Juvenile-onset SLE (jSLE) exhibits an aggressive clinical phenotype and severe complications. Dysregulated expression of microRNAs (miRs) in immune cells from patients with SLE has been found. We aim to evaluate the association of miR-125a with the clinical and laboratory characteristics, disease activity and inflammatory cytokines of jSLE patients. Methods 60 jSLE patients and 25 normal controls were involved in the study. The expression pattern of miR-125a was determined in plasma of all subjects using qRT-PCR. In addition, plasma levels of IL-17 and IFN-γ were examined using ELISA. The correlation of miR-125a expression with the clinical manifestations and disease activity of jSLE patients was analyzed. Also, its association with the inflammatory cytokines was investigated in jSLE patients. Results Our findings showed that miR-125a expression levels were significantly reduced in jSLE patients compared to normal controls ( p < 0.01) and these expression levels differed based on the clinical variability of patients. In addition, plasma levels of IL-17 and IFN-γ in jSLE patients were significantly higher than healthy controls ( p < 0.01). Finally, miR-125a expression had significant negative associations with each of SLEDAI-2K ( p < 0.01), SLICC ( p < 0.01), ESR ( p < 0.05), proteinuria ( p < 0.01) and IL-17 levels ( p < 0.01) in jSLE patients. Conclusion Our findings postulate that miR-125a could act as a candidate therapeutic target for its possible regulation of inflammation in jSLE patients.

Download Full-text

Soufeng sanjie formula alleviates collagen-induced arthritis in mice by inhibiting Th17 cell differentiation

Chinese Medicine ◽

10.1186/s13020-021-00448-9 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Di Hua ◽

Jie Yang ◽

Qinghai Meng ◽

Yuanyuan Ling ◽

Qin Wei ◽

...

Keyword(s):

Cell Differentiation ◽

Lymph Nodes ◽

Inflammatory Cytokines ◽

Th17 Cell ◽

Collagen Induced Arthritis ◽

Expression Levels ◽

Th17 Cell Differentiation ◽

Spleen And Lymph Nodes ◽

Seed Coats

Abstract Background Rheumatoid arthritis (RA) is a chronic autoimmune disease. Soufeng sanjie formula (SF), which is composed of scolopendra (dried body of Scolopendra subspinipes mutilans L. Koch), scorpion (dried body of Buthus martensii Karsch), astragali radix (dried root of Astragalus membranaceus (Fisch.) Bge), and black soybean seed coats (seed coats of Glycine max (L.) Merr), is a traditional Chinese prescription for treating RA. However, the mechanism of SF in treating RA remains unclear. This study was aim to investigate the anti-arthritic effects of SF in a collagen-induced arthritis (CIA) mouse model and explore the mechanism by which SF alleviates arthritis in CIA mice. Methods For in vivo studies, female DBA/1J mice were used to establish the CIA model, and either SF (183 or 550 mg/kg/day) or methotrexate (MTX, 920 mg/kg, twice/week) was orally administered to the mice from the day of arthritis onset. After administration for 30 days, degree of ankle joint destruction and serum levels of IgG and inflammatory cytokines were determined. The balance of Th17/Treg cells in the spleen and lymph nodes was analyzed using flow cytometry. Moreover, the expression levels of retinoic acid receptor-related orphan nuclear receptor (ROR) γt and phosphorylated STAT3 (pSTAT3, Tyr705) in the spleen were detected by immunohistochemistry. Furthermore, the effect of SF on Th17 cells differentiation in vitro was investigated in CD4+ T cells under Th17 polarization conditions. Results SF decreased the arthritis score, ameliorated paw swelling, and reduced cartilage loss in the joint of CIA mice. In addition, SF decreased the levels of bovine collagen-specific IgG in sera of CIA mice. SF decreased the levels of inflammatory cytokines (TNF-α, IL-6, and IL-17A) and increased the level of IL-10 both in the sera and the joint of CIA mice. Moreover, SF treatment rebalanced the Th17/Treg ratio in the spleen and lymph nodes of CIA mice. SF also reduced the expression levels of ROR γt and pSTAT3 (Tyr705) in the spleen of CIA mice. In vitro, SF treatment reduced Th17 cell generation and IL-17A production and inhibited the expression of RORγt, IRF4, IL-17A, and pSTAT3 (Tyr705) under Th17 polarization conditions. Conclusions Our results suggest that SF exhibits anti-arthritic effects and restores Th17/Treg homeostasis in CIA mice by inhibiting Th17 cell differentiation.

Download Full-text

Dynamic Evaluation of Compound Ento-PB for the Repair of Mucosal Ulcer in Dogs With Acetic Acid-induced Experimental Colitis

10.21203/rs.3.rs-127468/v1 ◽

2020 ◽

Author(s):

Jin-hu Chen ◽

Jian-ting Zhao ◽

Zheng-yong Yu ◽

Yi-hao Che ◽

Yu-jia Wang ◽

...

Keyword(s):

Ulcerative Colitis ◽

Acetic Acid ◽

Inflammatory Cytokines ◽

Mucosal Healing ◽

Dynamic Monitoring ◽

Enzyme Linked Immunosorbent Assay ◽

Dependent Manner ◽

Expression Levels ◽

Cox 2 ◽

Anti Inflammatory

Abstract Background: Mucosal inflammation and ulcer play important roles in the pathogenesis of ulcerative colitis. As as traditional Chinese medicine compound composed of Periplaneta americana and Taraxacum mongolicum, Ento-PB is always prescribed for the treatment of ulcer and inflammatory diseases. As for the significant role of P. americana in terms of promoting mucosal healing, the compatibility of the anti-inflammatory drug T. mongolicum may enable Ento-PB to simultaneously play anti-inflammatory and promote mucosal healing effects on the treatment of UC. Therefore, this study aimed to evaluate the therapeutic potential and possible mechanism of Ento-PB for UC by establishing an acetic acid-induced colitis model in dogs.Methods: Preliminary identification to the chemical components of compound Ento-PB was carried out through high performance liquid chromatography. A cross-bred dogs model of acetic acid-induced ulcerative colitis was established to evaluate the efficacy of compound Ento-PB. The expression levels of inflammatory cytokines C-reactive protein (CRP), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-10 (IL-10) in plasma were measured by carrying out enzyme-linked immunosorbent assay (ELISA).Results: With the extension of treatment time, Ento-PB could effectively improve clinical symptoms of UC cross-bred dogs. Colonoscopy displayed that mucosal redness, swelling and congestion decreased gradually, and obviously repaired after mucosal injury. The intestinal texture was gradually clear, and the colonoscopy score gradually reduced. Histopathological examination revealed that the structure of colon was restored significantly, the infiltration of inflammatory cells was reduced, and the histological score was remarkably reduced. At the same time, the results of dynamic monitoring of inflammatory cytokines in plasma proved that Ento-PB can gradually down-regulate the activity of CRP, iNOS and COX-2, reduce the expression levels of inflammatory cytokines TNF-α and IL-1β, and gradually restore anti-inflammatory and the expression level of cytokine IL-10.Conclusions: Ento-PB reduces the level of pro-inflammatory cytokines in a dose- and time-dependent manner and inflammation, improves colon tissue lesions and the repair of intestinal mucosa after injury, and effectively increases acetic acid-induced colon inflammation in UC cross-bred dogs.

Download Full-text

KS23, a novel peptide derived from adiponectin, inhibits retinal inflammation and downregulates the proportions of Th1 and Th17 cells during experimental autoimmune uveitis

Journal of Neuroinflammation ◽

10.1186/s12974-019-1686-y ◽

2019 ◽

Vol 16 (1) ◽

Cited By ~ 1

Author(s):

Tian Niu ◽

Lu Cheng ◽

Hanying Wang ◽

Shaopin Zhu ◽

Xiaolu Yang ◽

...

Keyword(s):

Inflammatory Cytokines ◽

Intraperitoneal Injection ◽

Chemokine Receptors ◽

Th17 Cells ◽

Experimental Autoimmune Uveitis ◽

Safe Alternative ◽

Autoimmune Uveitis ◽

Expression Levels ◽

Anti Inflammatory ◽

Experimental Autoimmune

Abstract Background Uveitis is a potentially sight-threatening form of ocular inflammation that affects the uvea in the wall of the eye. Currently available treatments for uveitis have exhibited profound adverse side effects. However, KS23 is a novel 23-amino-acid anti-inflammatory peptide derived from adiponectin that may have the capability to function as a safe alternative to these existing treatment options. We, therefore, evaluated the preventive effect of KS23 in experimental autoimmune uveitis (EAU). Methods EAU was induced in mice via immunization with the peptide interphotoreceptor retinoid binding protein 161–180 (IRBP161–180). KS23 was then administered every 2 days via intraperitoneal injection to induce protection against EAU. Clinical and histopathological scores were employed to evaluate the disease progression. Inflammatory cytokines were also quantified using ELISA, and the expression levels of specific chemokines and chemokine receptors were assessed via qRT-PCR. In addition, the proportions of Th1 and Th17 cells were detected via flow cytometry, and the expression levels of specific proteins were quantified from the retina of mice using western blot analysis, to elucidate the specific mechanism of action employed by KS23 to suppress the inflammation associated with EAU. Results KS23 was found to significantly improve EAU-associated histopathological scores, while decreasing the expression of pro-inflammatory cytokines (IFN-γ, TNF-α, IL-6, and IL-17A), chemokines (LARC, RANTES, MIG, IP-10), and chemokine receptors (CCR6 and CXCR3). The proportions of Th1 and Th17 cells were also suppressed following intraperitoneal injection with KS23. The anti-inflammatory mechanism employed by KS23 was determined to be associated with the activation of AMPK and subsequent inhibition of NF-κB. Conclusions KS23 decreased the proportions of Th1 and Th17 cells to effectively ameliorate the progression of EAU. It may, therefore, serve as a promising potential therapeutic agent for uveitis.

Download Full-text

Protective Effect of Resveratrol Improves Systemic Inflammation Responses in LPS-Injected Lambs

Animals ◽

10.3390/ani9110872 ◽

2019 ◽

Vol 9 (11) ◽

pp. 872 ◽

Cited By ~ 6

Author(s):

Yanping Liang ◽

Jianwei Zhou ◽

Kaixi Ji ◽

Hu Liu ◽

Allan Degen ◽

...

Keyword(s):

Inflammatory Cytokines ◽

Inflammatory Responses ◽

Clinical Symptoms ◽

Average Daily Gain ◽

Clinical Signs ◽

Blood Parameters ◽

Mapk Signaling ◽

Inflammatory Genes ◽

Expression Levels ◽

Daily Gain

Highly intensive livestock production often causes immune stress to animals, which makes them more susceptible to infections. The aim of this study was to examine whether resveratrol (Res) alleviates inflammation in lambs. In Experiment 1, 16 male lambs were injected with lipopolysaccharides (LPS) at an initial dose of 0.25, 1.25, and 2.5 μg/kg body weight (BW) for 9 days. Average daily gain and blood parameters were measured and clinical symptoms were recorded. In Experiment 2, 20 male lambs were injected intravenously with LPS (0 mg/kg) + Res (0 mg), LPS (2.5 μg /kg) + Res (0 mg, 82.5 mg, 165 mg, 330 mg), 4 h after LPS injection. Jugular blood was collected from each lamb to determine white blood cell (WBC) counts and the expression of inflammatory genes. In Experiment 1, all LPS-treated lambs showed clinical signs of sickness including rhinorrhea, lethargy, and shivering, and systemic inflammatory responses of increased inflammatory genes levels and cortisol concentration. The lambs had increased respiratory and heart rates and rectal temperature and decreased average daily gain and feed intake. In Experiment 2, resveratrol significantly reduced WBCs and the expression levels of several genes associated with inflammation response (TLR4, NF-κB, c-jun) and inhibited the signaling cascades of NF-κB and MAPKs by down-regulating the expression levels of inflammatory cytokines (IL-1β, IL-4, IL-6, TNF-α, IFN-γ) induced by LPS. Resveratrol attenuated the LPS-evoked inflammatory responses in lambs by suppressing expression levels of inflammatory cytokines, and blocking NF-κB and MAPK signaling pathways.

Download Full-text

Proinflammatory and Anti-Inflammatory Cytokines Mediated by NF-κB Factor as Prognostic Markers in Mammary Tumors

Mediators of Inflammation ◽

10.1155/2016/9512743 ◽

2016 ◽

Vol 2016 ◽

pp. 1-10 ◽

Cited By ~ 15

Author(s):

Gustavo Rodrigues Martins ◽

Gabriela Bottaro Gelaleti ◽

Marina Gobbe Moschetta ◽

Larissa Bazela Maschio-Signorini ◽

Debora Ap. Pires de Campos Zuccari

Keyword(s):

Protein Expression ◽

Survival Time ◽

Inflammatory Cytokines ◽

Prognostic Markers ◽

Tumor Development ◽

Mammary Tumors ◽

Clinicopathological Characteristics ◽

Expression Levels ◽

Gene And Protein Expression ◽

High Gene

Inflammation results in the production of cytokines, such as interleukin- (IL-) 4 and IL-10 with immunosuppressive properties or IL-6 and TNF-αwith procarcinogenic activity. Furthermore, NF-κB is the major link between inflammation and tumorigenesis. This study verified the interaction between active inflammatory cytokines in the tumor microenvironment and serum of female dogs with mammary tumors and their correlation with the clinicopathological characteristics and overall survival. Measurement of gene expression was performed by qPCR and protein levels by ELISA/Luminex. High gene and protein expression levels of NF-κB, IL-6, and TNF-αwere found in association with characteristics that reflect worse prognosis and a negative correlation between TNF-αprotein expression and survival time was observed (p<0.05). In contrast, high gene and protein expression levels of IL-4 and IL-10 were associated with characteristics of better prognosis and an increased level of IL-4 and a longer survival time of animals were obtained (p<0.05). In addition, there was a positive correlation between TNF-αand IL-6 expression in association with NF-κB. The results show a significant correlation of these cytokines with tumor development, associated with NF-κB expression and cytokines promodulation, showing that these biological factors could be used as predictive and prognostic markers in breast cancer.

Download Full-text

Environmental Enrichment Protects Offspring of a Rat Model of Preeclampsia from Cognitive Decline

10.21203/rs.3.rs-736215/v1 ◽

2021 ◽

Author(s):

Huiqing Lu ◽

Lili Gong ◽

Huangfang Xu ◽

Qiongjie Zhou ◽

Huanqiang Zhao ◽

...

Keyword(s):

Synaptic Plasticity ◽

Cognitive Ability ◽

Inflammatory Cytokines ◽

Spatial Learning ◽

Rat Model ◽

Environmental Enrichment ◽

Inflammatory Cytokine ◽

Hippocampal Neurogenesis ◽

Expression Levels ◽

Cytokine Levels

Abstract Background Preeclampsia affects 5–8% of all pregnancies and contributes to adverse pregnancy and birth outcomes. In addition to the short-term effects of preeclampsia, preeclampsia can exert long-term adverse effects on offspring. Numerous studies have demonstrated that offspring of preeclamptic women exhibit cognitive deficits from childhood to old age. However, effective ways to improve the cognitive abilities of these offspring remain to be investigated. The aim of this study was to explore whether environmental enrichment in early life could restore the cognitive ability of the offspring of a rat model of preeclampsia and to investigate the cellular and molecular mechanisms by which EE improves cognitive ability. Methods L-NAME was used to establish a rat model of preeclampsia. The spatial learning and memory abilities and recognition memory of 56-day-old offspring were evaluated by the Morris water maze and Novel object recognition (NOR) task. Immunofluorescence was performed to evaluate cell proliferation and apoptosis in the DG region of the hippocampus. qRT-PCR was performed to examine the expression levels of neurogenesis-associated genes, pre- and postsynaptic proteins and inflammatory cytokines. An enzyme-linked immune absorbent assay was performed to evaluate the concentration of vascular endothelial growth factor (VEGF) and inflammatory cytokines in the hippocampus. Results The administration of L-NAME led to increased systolic blood pressure and urine protein levels in pregnant rats. Offspring in the L-NAME group exhibited impaired spatial learning ability and memory as well as NOR memory. Hippocampal neurogenesis and synaptic plasticity were impaired in offspring from the L-NAME group. Furthermore, cell apoptosis in the hippocampus was increased in the L-NAME group. The hippocampus was skewed to a proinflammatory profile, as shown by increased inflammatory cytokine levels. EE improved the cognitive ability of offspring in the L-NAME group and resulted in increased hippocampal neurogenesis and synaptic protein expression levels and decreased apoptosis and inflammatory cytokine levels. Conclusions Environmental enrichment resolves cognitive impairment in the offspring of a rat model of preeclampsia by improving hippocampal neurogenesis and synaptic plasticity and normalizing the apoptosis level and the inflammatory balance.

Download Full-text

Anti-hyperalgesic properties of a flavanone derivative Poncirin in acute and chronic inflammatory pain models in mice

BMC Pharmacology and Toxicology ◽

10.1186/s40360-019-0335-5 ◽

2019 ◽

Vol 20 (1) ◽

Cited By ~ 4

Author(s):

Ruqayya Afridi ◽

Ashraf Ullah Khan ◽

Sidra Khalid ◽

Bushra Shal ◽

Hina Rasheed ◽

...

Keyword(s):

Acetic Acid ◽

Mrna Expression ◽

Inflammatory Cytokines ◽

Inflammatory Pain ◽

Expression Levels ◽

Chronic Inflammatory Pain ◽

Qrt Pcr ◽

Pain Models ◽

Anti Oxidant ◽

Mrna Expression Levels

Abstract Background Poncirin is flavanone derivative (isolated from Poncirus trifoliata) with known pharmacological activities such as anti-tumor, anti-osteoporotic, anti-inflammatory and anti-colitic. The present study aimed to explore the anti-allodynic and anti-hyperalgesic potentials of poncirin in murine models of inflammatory pain. Methods The analgesic potential of poncirin was evaluated in formalin-, acetic acid-, carrageenan- and Complete Freund’s Adjuvant (CFA)-induced inflammatory pain models in mice. Anti-allodynic and anti-hyperalgesic activities were measured using Von Frey filaments, Randall Selitto, hotplate and cold acetone tests. The serum nitrite levels were determined using Griess reagent. The Quantitative Real-time PCR (qRT-PCR) was performed to assess the effect of poncirin on mRNA expression levels of inflammatory cytokines and anti-oxidant enzymes. Results Intraperitoneal administration of poncirin (30 mg/kg) markedly reduced the pain behavior in both acetic acid-induced visceral pain and formalin-induced tonic pain models used as preliminary screening tools. The poncirin (30 mg/kg) treatment considerably inhibited the mechanical hyperalgesia and allodynia as well as thermal hyperalgesia and cold allodynia. The qRT-PCR analysis showed noticeable inhibition of pro-inflammatory cytokines (mRNA expression levels of TNF-α, IL-1β and IL-6) (p < 0.05) in poncirin treated group. Similarly, poncirin treatment also enhanced the mRNA expressions levels of anti-oxidant enzymes such as transcription factor such as nuclear factor (erythroid-derived 2)-like 2 (Nrf2) (p < 0.05), heme oxygenase (HO-1) (p < 0.05) and superoxide dismutase (SOD2) (p < 0.05). Chronic treatment of poncirin for 6 days did not confer any significant hepatic and renal toxicity. Furthermore, poncirin treatment did not altered the motor coordination and muscle strength in CFA-induced chronic inflammatory pain model. Conclusion The present study demonstrated that poncirin treatment significantly reduced pain behaviors in all experimental models of inflammatory pain, suggesting the promising analgesic potential of poncirin in inflammatory pain conditions.

Download Full-text

MicroRNA-322 inhibits inflammatory cytokine expression and promotes cell proliferation in LPS-stimulated murine macrophages by targeting NF-κB1 (p50)

Bioscience Reports ◽

10.1042/bsr20160239 ◽

2017 ◽

Vol 37 (1) ◽

Cited By ~ 13

Author(s):

Kai Zhang ◽

Fengling Song ◽

Xiaoxia Lu ◽

Wenxun Chen ◽

Chunxiao Huang ◽

...

Keyword(s):

Cell Cycle ◽

Inflammatory Response ◽

Inflammatory Cytokines ◽

Cell Cycle Progression ◽

Negative Regulator ◽

Luciferase Assay ◽

Raw264.7 Cells ◽

Expression Levels ◽

Pathogen Invasion ◽

Lps Treatment

Inflammation is the body’s normal self-protection mechanism to eliminate pathogens and resist pathogen invasion. The excessive inflammatory response may lead to inflammatory lesions. The mechanisms accounting for inflammation remain hazy. miRNAs have been proposed to have crucial effects on inflammation. In the present study, we reported that lipopolysaccharide (LPS)-stimulation increased the expression levels of inflammatory cytokines and the cell-cycle progression was suppressed in RAW264.7 cells. Meanwhile, the expression of miR-322 was significantly down-regulated after LPS treatment. Bioinformatics predictions revealed a potential binding site of miR-322 in 3′-UTR of NF-κB1 (p50) and it was further confirmed by luciferase assay. Moreover, both the mRNA and protein levels of NF-κB1 (p50) were down-regulated by miR-322 in RAW264.7 cells. Subsequently, we demonstrated that miR-322 mimics decrease in the expression levels of inflammatory cytokines and cell-cycle repression can be rescued following LPS treatment in RAW264.7 cells. The anti-inflammatory cytokines expression including IL-4 and IL-10 were significantly up-regulated. Furthermore, miR-322 could also promote RAW264.7 cells proliferation. These results demonstrate that miR-322 is a negative regulator of inflammatory response by targeting NF-κB1 (p50).

Download Full-text