GBP1 exerts inhibitory effects on acute viral myocarditis by inhibiting the inflammatory response of macrophages in mice

Viral myocarditis (VMC) is a condition that could potentially progress to dilated cardiomyopathy or congestive heart failure, making it the leading cause of the untimely death in young adults. Interferon-induced GBP1 encodes much of the GTPase induced by interferon gamma in many eukaryotic cells. However, little is known regarding the effect of GBP1 on acute VMC (AVMC). Hence, this aim of this study was to assess the effect of GBP1 on AVMC. Once the AVMC mouse models were established, the functional role of GBP1 was determined in AVMC. Serum levels of IL-6, TNF-α, and TGF-β, and expression levels of GBP1, MIF, iNOS, and COX-2 were detected, together with the viability and apoptosis of cardiomyocytes. AVMC mice presented with increased levels of TGF-β, IL-6, TNF-α, MIF, iNOS, and COX-2, as well as cell apoptosis, but lower expression of GBP1 and viability of cardiomyocytes. Restored GBP1 or depleted macrophages resulted in decreased levels of TGF-β, IL-6, TNF-α, MIF, iNOS, and COX-2, as well as cardiomyocyte apoptosis, while increasing cardiomyocyte viability. In conclusion, our results highlight the potential role of GBP1 in inhibiting AVMC development. The experimental results indicate that GBP1 up-regulation and macrophage depletion can alleviate AVMC-related cardial damage by inhibiting inflammatory responses and cardiomyocyte apoptosis while increasing cardiomyocyte viability.

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TNF-induced IL-8 and MCP-1 production in the eosinophilic cell line, EOL-1

Mediators of Inflammation ◽

10.1155/s0962935196000312 ◽

1996 ◽

Vol 5 (3) ◽

pp. 218-223 ◽

Cited By ~ 9

Author(s):

L. A. Goldstein ◽

R. M. Strieter ◽

H. L. Evanoff ◽

S. L. Kunkel ◽

N. W. Lukacs

Keyword(s):

Cell Line ◽

Inflammatory Responses ◽

Kinetic Studies ◽

Inhibitory Effects ◽

Chemokine Production ◽

Eosinophil Cell ◽

Tnf Α ◽

Eosinophilic Cell ◽

Suppressive Cytokine

The role of eosinophils in inflammation and their mode of activation is not well understood. Eosinophil accumulation and subsequent expression of cytokines at the site of inflammation may play a role in exacerbation of inflammatory responses. In the present study, we have examined the role of TNF-α in eosinophil activation and chemokine production using a human leukaemic eosinophil cell line, EOL-1. Initial studies demonstrated that TNF-α induced the upregulation of IL-8 and MCP-1 mRNA and protein. Kinetic studies indicated production of chemokines, IL-8 and MCP-1, as early as 4 h post-activation, with peak levels of chemokine produced at 8 h, and decreasing by 24 h post-TNF-α activation. When IL-10, a suppressive cytokine, was incubated with TNF-α and EOL-1 cells, no effect was observed on IL-8 and MCP-1 production. However, dexamethasone, a glucocorticoid, demonstrated potent inhibitory effects on the EOL-1-derived chemokines. These studies indicate that eosinophils may be a significant source of chemokines capable of participating in, and maintaining, leukocyte recruitment during inflammatory responses, such as asthma.

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In Vitro Evaluation of the Anti-Inflammatory Effect of KMUP-1 and in Vivo Analysis of Its Therapeutic Potential in Osteoarthritis

Biomedicines ◽

10.3390/biomedicines9060615 ◽

2021 ◽

Vol 9 (6) ◽

pp. 615

Author(s):

Shang-En Huang ◽

Erna Sulistyowati ◽

Yu-Ying Chao ◽

Bin-Nan Wu ◽

Zen-Kong Dai ◽

...

Keyword(s):

Articular Cartilage ◽

Inflammatory Responses ◽

Therapeutic Potential ◽

Antioxidant Properties ◽

Serum Levels ◽

Gene Expressions ◽

Tnf Α ◽

Anti Inflammatory

Osteoarthritis is a degenerative arthropathy that is mainly characterized by dysregulation of inflammatory responses. KMUP-1, a derived chemical synthetic of xanthine, has been shown to have anti-inflammatory and antioxidant properties. Here, we aimed to investigate the in vitro anti-inflammatory and in vivo anti-osteoarthritis effects of KMUP-1. Protein and gene expressions of inflammation markers were determined by ELISA, Western blotting and microarray, respectively. RAW264.7 mouse macrophages were cultured and pretreated with KMUP-1 (1, 5, 10 μM). The productions of TNF-α, IL-6, MMP-2 and MMP- 9 were reduced by KMUP-1 pretreatment in LPS-induced inflammation of RAW264.7 cells. The expressions of iNOS, TNF-α, COX-2, MMP-2 and MMP-9 were also inhibited by KMUP-1 pretreatment. The gene expression levels of TNF and COX families were also downregulated. In addition, KMUP-1 suppressed the activations of ERK, JNK and p38 as well as phosphorylation of IκBα/NF-κB signaling pathways. Furthermore, SIRT1 inhibitor attenuated the inhibitory effect of KMUP-1 in LPS-induced NF-κB activation. In vivo study showed that KMUP-1 reduced mechanical hyperalgesia in monoiodoacetic acid (MIA)-induced rats OA. Additionally, KMUP-1 pretreatment reduced the serum levels of TNF-α and IL-6 in MIA-injected rats. Moreover, macroscopic and histological observation showed that KMUP-1 reduced articular cartilage erosion in rats. Our results demonstrated that KMUP-1 inhibited the inflammatory responses and restored SIRT1 in vitro, alleviated joint-related pain and cartilage destruction in vivo. Taken together, KMUP-1 has the potential to improve MIA-induced articular cartilage degradation by inhibiting the levels and expression of inflammatory mediators suggesting that KMUP-1 might be a potential therapeutic agent for OA.

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Role of endogenous TNF-α in cardiomyocyte apoptosis induced by bacteria lipoprotein and the protective effect of IL-10

European Journal of Inflammation ◽

10.1177/1721727x15597363 ◽

2015 ◽

Vol 13 (2) ◽

pp. 117-125 ◽

Cited By ~ 3

Author(s):

Zhicai Li ◽

Jing Zhou ◽

Dongmei Zhu ◽

Qian Zhang ◽

Min Huang ◽

...

Keyword(s):

Protective Effect ◽

Cardiomyocyte Apoptosis ◽

Tnf Α

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Evaluation of serum ATX and LPA as potential diagnostic biomarkers in patients with pancreatic cancer

BMC Gastroenterology ◽

10.1186/s12876-021-01635-6 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Jiang Chen ◽

Hongyu Li ◽

Wenda Xu ◽

Xiaozhong Guo

Keyword(s):

Pancreatic Cancer ◽

Poor Prognosis ◽

Prognostic Value ◽

Potential Role ◽

Early Stage ◽

Serum Levels ◽

Diagnostic Efficacy ◽

Diagnostic Biomarkers ◽

The Poor

Abstract Background Pancreatic cancer (PC) is a devastating disease that has a poor prognosis and a total 5-year survival rate of around 5%. The poor prognosis of PC is due in part to a lack of suitable biomarkers that can allow early diagnosis. The lysophospholipase autotaxin (ATX) and its product lysophosphatidic acid (LPA) play an essential role in disease progression in PC patients and are associated with increased morbidity in several types of cancer. In this study, we evaluated both the potential role of serum LPA and ATX as diagnostic markers in PC and their prognostic value for PC either alone or in combination with CA19-9. Methods ATX, LPA and CA19-9 levels were evaluated using ELISA of serum obtained from PC patients (n = 114) healthy volunteers (HVs: n = 120) and patients with benign pancreatic diseases (BPDs: n = 94). Results Serum levels of ATX, LPA and CA19-9 in PC patients were substantially higher than that for BPD patients or HVs (p < 0.001). The sensitivity of LPA in early phase PC was 91.74% and the specificity of ATX was 80%. The levels of ATX, LPA and CA19-9 were all substantially higher for early stage PC patients compared to levels in serum from BPD patients and HVs. The diagnostic efficacy of CA19-9 for PC was significantly enhanced by the addition of ATX and LPA (p = 0.0012). Conclusion Measurement of LPA and ATX levels together with CA19-9 levels can be used for early detection of PC and diagnosis of PC in general.

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Social Stressors, Arboviral Infection, and Immune Dysregulation in the Coastal Lowland Region of Ecuador: A Mixed Methods Approach in Ecological Perspective

American Journal of Tropical Medicine and Hygiene ◽

10.4269/ajtmh.20-1625 ◽

2021 ◽

Author(s):

Denisse Vega Ocasio ◽

Anna M. Stewart-Ibarra ◽

Rachel Sippy ◽

Christina Li ◽

Kaitlyn McCue ◽

...

Keyword(s):

At Risk ◽

Immune Responses ◽

Inflammatory Responses ◽

Social Stressors ◽

Biological Responses ◽

Distress Symptoms ◽

Tnf Α ◽

Hair Samples ◽

Arboviral Diseases

Aedes aegypti, the mosquito that transmits arboviral diseases such as dengue (DENV), chikungunya (CHIKV), and Zika viruses (ZIKV), is present in tropical and subtropical regions of the world. Individuals at risk of mosquito-borne disease (MBD) in the urban tropics face daily challenges linked to their socio-environment conditions, such as poor infrastructure, poverty, crowding, and limited access to adequate healthcare. These daily demands induce chronic stress events and dysregulated immune responses. We sought to investigate the role of socio-ecologic risk factors in distress symptoms and their impact on biological responses to MBD in Machala, Ecuador. Between 2017 and 2019, individuals (≥ 18 years) with suspected arbovirus illness (DENV, ZIKV, and CHIKV) from sentinel clinics were enrolled (index cases, N = 28). Cluster investigations of the index case households and people from four houses within a 200-m radius of index home (associate cases, N = 144) were conducted (total N = 172). Hair samples were collected to measure hair cortisol concentration (HCC) as a stress biomarker. Blood samples were collected to measure serum cytokines concentrations of IL-10, IL-8, TNF-α, and TGF-β. Univariate analyses were used to determine the association of socio-health metrics related to perceived stress scores (PSS), HCC, and immune responses. We found that housing conditions influence PSS and HCC levels in individuals at risk of MBD. Inflammatory cytokine distribution was associated with the restorative phase of immune responses in individuals with low-moderate HCC. These data suggest that cortisol may dampen pro-inflammatory responses and influence activation of the restorative phase of immune responses to arboviral infections.

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3-methyadenine inhibits lipopolysaccharides-induced pulmonary inflammation at the early stage of silicosis via blocking NF-κB signaling pathway

Toxicology and Industrial Health ◽

10.1177/07482337211039426 ◽

2021 ◽

pp. 074823372110394

Author(s):

Yujing Zhang ◽

Shuai Huang ◽

Shiyi Tan ◽

Mingke Chen ◽

Shang Yang ◽

...

Keyword(s):

Lung Injury ◽

Late Stage ◽

Caspase 3 ◽

Inflammatory Responses ◽

Early Stage ◽

Pulmonary Inflammation ◽

Mechanism Study ◽

Silica Dust ◽

Tnf Α

Occupational exposure to silica dust is related to pulmonary inflammation and silicosis. Lipopolysaccharides (LPSs) could aggravate apoptosis in alveolar macrophages (AMs) of human silicosis through autophagy, yet how the reduction of autophagy attenuated LPS-induced lung injury and the related mechanisms need to be investigated. In the study, we aim to understand the role of 3-methyladenine (3-MA), an inhibitor of autophagy, in LPS-mediated inflammatory responses and fibrosis. We collected AMs from observers/silicosis patients. The results showed that LPS induced NF-κB-related pulmonary inflammation in observers and silicosis patients, as confirmed by an increase in the expression of IL-1β, IL-6, TNF-α, and p65, which could be inhibited by 3-MA treatment. In mice models, at the early stage (7d) of silicosis, but not the late (28d) stage, blocking autophagy reversed the increased levels of IL-1β, IL-6, TNF-α, and p65 caused by LPS. Mechanism study revealed that LPS triggered the expression of LC3 II, p62, and cleaved caspase-3 at the early stage exposed to silica, which could be restored by 3-MA, while there was no difference in the expression of LAMP1 either at the early or late stage of silicosis in different groups. Similarly, 3-MA treatment did not prevent fibrosis characterized by destroyed alveoli, collagen deposition, and increased expression of α-SMA and Col-1 induced by LPS at the late stage of silicosis. The results suggested that 3-MA has a role in the protection of lung injury at the early stage of silicosis and provided an experimental basis for preventive strategies of pulmonary inflammation and silicosis.

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The Antioxidant Effects of Isorhamnetin Contribute to Inhibit COX-2 Expression in Response to Inflammation: A Potential Role of HO-1

Inflammation ◽

10.1007/s10753-013-9789-6 ◽

2013 ◽

Vol 37 (3) ◽

pp. 712-722 ◽

Cited By ~ 36

Author(s):

Kyuhwa Seo ◽

Ji Hye Yang ◽

Sang Chan Kim ◽

Sae Kwang Ku ◽

Sung Hwan Ki ◽

...

Keyword(s):

Potential Role ◽

Cox 2 ◽

Antioxidant Effects

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Proinflammatory responses in SARS-CoV-2 infected and soluble spike glycoprotein S1 subunit activated human macrophages

10.1101/2021.06.14.448426 ◽

2021 ◽

Author(s):

Kim Chiok ◽

Kevin Hutchison ◽

Lindsay Grace Miller ◽

Santanu Bose ◽

Tanya A Miura

Keyword(s):

Virus Infection ◽

Inflammatory Response ◽

Virus Replication ◽

Inflammatory Mediators ◽

Inflammatory Responses ◽

Activated Macrophages ◽

Human Macrophages ◽

Tnf Α ◽

Proinflammatory Responses

Critically ill COVID-19 patients infected with SARS-CoV-2 display signs of generalized hyperinflammation. Macrophages trigger inflammation to eliminate pathogens and repair tissue, but this process can also lead to hyperinflammation and resulting exaggerated disease. The role of macrophages in dysregulated inflammation during SARS-CoV-2 infection is poorly understood. We used SARS-CoV-2 infected and glycosylated soluble SARS-CoV-2 Spike S1 subunit (S1) treated THP-1 human-derived macrophage-like cell line to clarify the role of macrophages in pro-inflammatory responses. Soluble S1 upregulated TNF-α and CXCL10 mRNAs, and induced secretion of TNF-α from THP-1 macrophages. While THP-1 macrophages did not support productive SARS-CoV-2 replication, virus infection resulted in upregulation of both TNF-α and CXCL10 genes. Our study shows that S1 is a key viral component inducing inflammatory response in macrophages, independently of virus replication. Thus, virus-infected or soluble S1-activated macrophages may become sources of pro-inflammatory mediators contributing to hyperinflammation in COVID-19 patients.

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In Silico Insight the Prediction of Chlorogenic Acid in Coffee through Cyclooxygenase-2 (COX2) Interaction

Biogenesis Jurnal Ilmiah Biologi ◽

10.24252/bio.v7i2.9847 ◽

2019 ◽

Vol 7 (2) ◽

Author(s):

Yohanes Bare ◽

Dewi Ratih Tirto Sari ◽

Yoga Tribakti Rachmad ◽

Gabriella Candrakirana Krisnamurti ◽

Agustina Elizabeth

Keyword(s):

Chlorogenic Acid ◽

Potential Role ◽

Interaction Model ◽

Data Bank ◽

High Permeability ◽

Discovery Studio ◽

Docking Approach ◽

Cox 2 ◽

Therapeutic Compound

Inflammation was signs of pathological or abnormality in tissue to give an alert as a trouble signal to the system. Therapeutic using NSAIDs has some side effects. This research explored the potential role of chlorogenic acid as natural therapeutic compound to inhibit the inflammation target such as COX-2 by interaction model. The research method used in this study was the molecular docking approach, which binds ligand and protein. Protein data provided by Protein Data Bank (ID: 6cox) while, chlorogenic acid obtain from PubChem (CID: 1794427). We docked COX-2 and chlorogenic acid using Hex 8.0.0. Visualization and analysis of the molecular interactions of chlorogenic acid and COX-2 conducted by the Discovery Studio Client 4.1 software. Chlorogenic acid has a high permeability and is easily absorbed based on five Lipinski Rule. Interestingly, we found Fifteen amino acid was binding with chlorogenic acid that formed by hydrogen bond and van der Waals.The interaction between ligand-protein results in energy binding -327.59cal/mol. Chlorogenic acid has a potential role to inhibit inflammation pathway by inhibiting COX-2. We predicted chlorogenic acid has a potential as therapy anti-inflammatory to suppress COX-2 as mediator inflammation.

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The Anti-Inflammatory Potential of Mimosa caesalpiniifolia Following Experimental Colitis: Role of COX-2 and TNF-Alpha Expression

Drug Research ◽

10.1055/s-0043-119750 ◽

2017 ◽

Vol 68 (04) ◽

pp. 196-204 ◽

Cited By ~ 3

Author(s):

Marcelo Silva ◽

Wagner Vilegas ◽

Marcelo da Silva ◽

Ana Paiotti ◽

Mauricio Pastrelo ◽

...

Keyword(s):

Protective Action ◽

Experimental Colitis ◽

Distal Colon ◽

Tnf Alpha ◽

High Dose ◽

Dependent Manner ◽

Hydroalcoholic Extract ◽

Tnf Α ◽

Cox 2

AbstractThe aim of this study was to evaluate the preventive and/or protective action of Mimosa caesalpiniifolia (M. caesalpiniifolia) following experimental colitis in rats. The rats were randomized into ten groups (n=10 per group), as follows: G1 – Sham group:; G2 – TNBS group; G3, G4 –colitis and treated with hydroalcoholic extract of M. caesalpiniifolia 250 mg/kg/day after and before/after inducing colitis, respectively; G5, G6 – colitis and treated with hydroalcoholic extract of M. caesalpiniifolia at 125 mg/kg/day after and before/after inducing colitis respectively; G7,G8 – colitis and treated with ethylacetate fraction of M. caesalpiniifolia at 50 mg/kg/day after and before/after inducing colitis, respectively; G9,G10 – colitis and treated with ethylacetate fraction of M. caesalpiniifolia at 50 mg/kg/day after and before/after inducing colitis, respectively. Rats treated with hydroalcoholic extract of M. caesalpiniifolia for both doses showed lower tissue damage in the distal colon. Ethylacetate fraction was effective at the highest dose only when administrated after inducing colitis. A downregulation of COX-2 was detected to rats suffering colitis and treated with M. caesalpiniifolia at high dose. On the other hand, TNF-alpha immunoexpression decreased in groups treated with M. caesalpiniifolia at low dose after inducing colitis. In summary, our results suggest that M. caesalpiniifolia attenuated the lesions of the colon, reduced inflammation, and modulates the expression of COX-2 and TNF-α during chronic colitis induced by TNBS when using for therapeutic purposes on a dose-dependent manner.

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