Regulation of the IL-33/ST2 Pathway Contributes to the Anti-Inflammatory Effect of Acupuncture in the Ovalbumin-Induced Murine Asthma Model

2018 ◽  
Vol 36 (5) ◽  
pp. 319-326 ◽  
Author(s):  
Ming Dong ◽  
Cheng Ma ◽  
Wen-Qian Wang ◽  
Juan Chen ◽  
Ying Wei
Keyword(s):  
Lung Function ◽  
Mouse Model ◽  
Chronic Inflammation ◽  
Bronchial Asthma ◽  
Acupuncture Treatment ◽  
Dynamic Compliance ◽  
Mucus Secretion ◽  
Asthma Model ◽  
Tnf Α ◽  
Murine Asthma Model

Background Bronchial asthma is a chronic airway inflammatory disease which has three main pathological features: airway hyperresponsiveness (AHR), airway remodelling, and chronic inflammation. Acupuncture is known to be an effective integrative medical therapy that has been used in the treatment of several chronic diseases, including bronchial asthma. The aim of the current study was to evaluate the effects of acupuncture on inflammation and regulation of the IL-33/ST2 pathway in a mouse model of asthma. Methods The murine asthma model was established by both injection and inhalation of ovalbumin (OVA). Within 24 hours of the last OVA challenge, lung function was assessed by measurement of the airway resistance (RL) and lung dynamic compliance (Cdyn). Pulmonary tissues were collected for the detection of pathological changes and mucus secretion. Serum levels of tumour necrosis factor α (TNF-α), interleukin (IL)-1β, IL-33 and sST2 (secreted ST2) were detected by ELISA. Th17 cell proportions and counts in bronchoalveolar lavage fluid (BALF) were analysed by flow cytometry. Results The results showed that AHR, chronic inflammation and mucus secretion were significantly suppressed by acupuncture treatment. RL decreased while Cdyn increased after acupuncture treatment. There was an apparent decrease in the serum concentrations of certain pro-inflammatory cytokines, such as TNF-α, IL-1β and IL-33, and an increase in sST2 level compared with untreated asthmatic mice. Acupuncture also reduced the CD4 +IL-17A+ cell proportion and counts in BALF. Conclusion Acupuncture effectively protects lung function and attenuates airway inflammation in the OVA-induced mouse model of asthma, which supports the role of acupuncture as a potential therapy in asthma treatment.

Elevated level of circulatory sTLT1 induces inflammation through SYK/MEK/ERK signalling in coronary artery disease

2019 ◽  
Vol 133 (22) ◽  
pp. 2283-2299
Author(s):  
Apabrita Ayan Das ◽  
Devasmita Chakravarty ◽  
Debmalya Bhunia ◽  
Surajit Ghosh ◽  
Prakash C. Mandal ◽  
...  
Keyword(s):  
Risk Factors ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Chronic Inflammation ◽  
Ex Vivo ◽  
Human Subjects ◽  
Critical Role ◽  
Atherosclerotic Cardiovascular Disease ◽  
Tnf Α ◽  
Artery Disease

Abstract The role of inflammation in all phases of atherosclerotic process is well established and soluble TREM-like transcript 1 (sTLT1) is reported to be associated with chronic inflammation. Yet, no information is available about the involvement of sTLT1 in atherosclerotic cardiovascular disease. Present study was undertaken to determine the pathophysiological significance of sTLT1 in atherosclerosis by employing an observational study on human subjects (n=117) followed by experiments in human macrophages and atherosclerotic apolipoprotein E (apoE)−/− mice. Plasma level of sTLT1 was found to be significantly (P<0.05) higher in clinical (2342 ± 184 pg/ml) and subclinical cases (1773 ± 118 pg/ml) than healthy controls (461 ± 57 pg/ml). Moreover, statistical analyses further indicated that sTLT1 was not only associated with common risk factors for Coronary Artery Disease (CAD) in both clinical and subclinical groups but also strongly correlated with disease severity. Ex vivo studies on macrophages showed that sTLT1 interacts with Fcɣ receptor I (FcɣRI) to activate spleen tyrosine kinase (SYK)-mediated downstream MAP kinase signalling cascade to activate nuclear factor-κ B (NF-kB). Activation of NF-kB induces secretion of tumour necrosis factor-α (TNF-α) from macrophage cells that plays pivotal role in governing the persistence of chronic inflammation. Atherosclerotic apoE−/− mice also showed high levels of sTLT1 and TNF-α in nearly occluded aortic stage indicating the contribution of sTLT1 in inflammation. Our results clearly demonstrate that sTLT1 is clinically related to the risk factors of CAD. We also showed that binding of sTLT1 with macrophage membrane receptor, FcɣR1 initiates inflammatory signals in macrophages suggesting its critical role in thrombus development and atherosclerosis.

Role of inflammation in the development of colorectal cancer

2020 ◽  
Vol 20 ◽  
Author(s):  
Sridhar Muthusami ◽  
R. Ileng Kumaran ◽  
Kokelavani Nampalli Babu ◽  
Sneha Krishnamoorthy ◽  
Akash Guruswamy ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Chronic Inflammation ◽  
Interleukin 1 ◽  
Cell Types ◽  
Model Systems ◽  
Cytokine Gene Expression ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Proinflammatory Molecules

: Chronic inflammation can lead to the development of many diseases including cancer. Inflammatory bowel disease (IBD) that includes both ulcerative colitis (UC) and Crohn's disease (CD) are risk factors for the development of colorectal cancer (CRC). Many cytokines produced primarily by the gut immune cells either during or in response to localized inflammation in the colon and rectum are known to stimulate the complex interactions between the different cell types in the gut environment resulting in acute inflammation. Subsequently, chronic inflammation together with genetic and epigenetic changes has been shown to lead to the development and progression of CRC. Various cell types present in the colon such as enterocytes, Paneth cells, goblet cells and macrophages express receptors for inflammatory cytokines and respond to tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), IL-6 and other cytokines. Among the several cytokines produced, TNF-α and IL-1β are the key proinflammatory molecules that play critical roles in the development of CRC. The current review is intended to consolidate the published findings to focus on the role of proinflammatory cytokines, namely TNF-α and IL-1β, on inflammation (and the altered immune response) in the gut, to better understand the development of CRC in IBD, using various experimental model systems, preclinical and clinical studies. Moreover, this review also highlights the current therapeutic strategies available (monotherapy and combination therapy), to alleviate the symptoms or treat inflammationassociated CRC by using monoclonal antibodies or aptamers to block proinflammatory molecules, inhibitors of tyrosine kinases in inflammatory signaling cascade, competitive inhibitors of proinflammatory molecules, and the nucleic acid drugs like small activating RNAs (saRNAs) or microRNA (miRNA) mimics to activate tumor suppressor or repress oncogene/proinflammatory cytokine gene expression.

scholarly journals Chronic Inflammation in PCOS: The Potential Benefits of Specialized Pro-Resolving Lipid Mediators (SPMs) in the Improvement of the Resolutive Response

2020 ◽  
Vol 22 (1) ◽  
pp. 384
Author(s):  
Pedro-Antonio Regidor ◽  
Anna Mueller ◽  
Manuela Sailer ◽  
Fernando Gonzalez Santos ◽  
Jose Miguel Rizo ◽  
...  
Keyword(s):  
Chronic Inflammation ◽  
Unsaturated Fatty Acids ◽  
Inflammatory Diseases ◽  
Reproductive Age ◽  
Lipid Mediator ◽  
Female Population ◽  
Tnf Α ◽  
Potential Benefits ◽  
Cardinal Symptoms ◽  
Resolution Processes

PCOS as the most common endocrine disorder of women in their reproductive age affects between 5–15% of the female population. Apart from its cardinal symptoms, like irregular and anovulatory cycles, hyperandrogenemia and a typical ultrasound feature of the ovary, obesity, and insulin resistance are often associated with the disease. Furthermore, PCOS represents a status of chronic inflammation with permanently elevated levels of inflammatory markers including IL-6 and IL-18, TNF-α, and CRP. Inflammation, as discovered only recently, consists of two processes occurring concomitantly: active initiation, involving “classical” mediators including prostaglandins and leukotrienes, and active resolution processes based on the action of so-called specialized pro-resolving mediators (SPMs). These novel lipid mediator molecules derive from the essential ω3-poly-unsaturated fatty acids (PUFAs) DHA and EPA and are synthesized via specific intermediates. The role and benefits of SPMs in chronic inflammatory diseases like obesity, atherosclerosis, and Diabetes mellitus has become a subject of intense research during the last years and since PCOS features several of these pathologies, this review aims at summarizing potential roles of SPMs in this disease and their putative use as novel therapeutics.

scholarly journals Reduced Lung Function in a Chronic Asthma Model Is Associated with Prolonged Inflammation, but Independent of Peribronchial Fibrosis

PLoS ONE ◽  
2008 ◽  
Vol 3 (2) ◽  
pp. e1575 ◽  
Author(s):  
Cordula Koerner-Rettberg ◽  
Sandra Doths ◽  
Anke Stroet ◽  
Jürgen Schwarze
Keyword(s):  
Lung Function ◽  
Chronic Asthma ◽  
Asthma Model

scholarly journals Regulation of TREM1-Mediated Inflammation in Hepatocellular Carcinoma Cells

Reports ◽  
2021 ◽  
Vol 4 (2) ◽  
pp. 17
Author(s):  
Vikrant Rai ◽  
Devendra K. Agrawal
Keyword(s):  
Hepatocellular Carcinoma ◽  
Vitamin D ◽  
Chronic Inflammation ◽  
Therapeutic Target ◽  
Primary Liver Cancer ◽  
Migration And Invasion ◽  
Potential Therapeutic Target ◽  
Mediators Of Inflammation ◽  
Tnf Α ◽  
Hcc Cells

Hepatocellular carcinoma (HCC), accounting for more than 90% of cases of primary liver cancer, is the third most common cause of cancer-related death worldwide. Chronic inflammation precedes the development of cirrhosis and HCC. TREM (triggering receptor expressed on myeloid cell)-1 is an inflammatory marker and amplifier of inflammation that signals through PI3K and ERK1/2 to activate transcription factors, resulting in increased secretion of pro-inflammatory cytokines, causing chronic inflammation and predisposing the liver to carcinogenesis. Thus, targeting TREM-1 in HCC might be a potential therapeutic target. A low level of vitamin D has been associated with chronic inflammation and poor prognosis in HCC. Thus, we evaluated the effect of vitamin D on TREM-1 expression in the HCC cell line. Additionally, the effects of high mobility group box-1, lipopolysaccharide, and transcription factor PU.1 on the expression of TREM-1 in normal liver cells and HCC cells have been investigated in the presence and absence of vitamin D. The results showed increased expression of TREM-1 in HCC cells and with IL-6, TNF-α, LPS, and rHMGB-1 and decreased expression with calcitriol. Calcitriol also attenuated the effect of IL-6, TNF-α, LPS, and rHMGB-1 on TREM-1. Calcitriol treatment attenuated the proliferation, migration, and invasion of HCC cells. These results (in vitro) provide molecular and biochemical evidence that calcitriol significantly attenuates the expression of mediators of inflammation, and thus might be used therapeutically together with conventional treatment to delay the progression of HCC. Additionally, the negative regulation of TREM-1 by PU.1 suggests PU.1 as a potential therapeutic target.

scholarly journals Regulatory Effects of Nur77 on Airway Remodeling and ASMC Proliferation in House Dust Mite-Induced Asthma

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Kun Wang ◽  
Muyun Wang ◽  
Yan Shang ◽  
Yanan He ◽  
Qiang Li ◽  
...  
Keyword(s):  
Chronic Inflammation ◽  
Lung Diseases ◽  
Airway Remodeling ◽  
Vital Role ◽  
Cell Hyperplasia ◽  
Asthma Model ◽  
Dust Mite ◽  
Asthma Patients ◽  
Antioxidant Gene Expression ◽  
Regulatory Effects

Airway remodeling played a vital role in the development of asthma, and airway smooth muscle (ASM) mass was its hallmark. However, few strategies targeting ASM remodeling were developed in treating asthma. Nur77 was the transcription factor nuclear receptor involved in the pathogenesis of several lung diseases. Nur77 distribution and expression were determined in an HDM-mediated allergic asthma model. Its effect on airway hyperresponsiveness (AHR), chronic inflammation, and ASM remodeling in asthmatic mice was evaluated using a lentivirus-mediated shRNA. Possible mechanisms were explored by examining Nur77 actions and its underlying pathways in primary human AMC cells (ASMCs). In this study, we reported that Nur77 expression was mainly distributed along ASM and increased in lungs of HDM-challenged mice. Nur77 depletion by lentivirus-mediated shRNA ameliorated AHR, chronic inflammation, goblet cell hyperplasia, and airway remodeling in the asthmatic mouse model. By means of primary human ASMC, we discovered that Nur77 upregulation by HDM stimulation promoted cell proliferation and ROS production, as well as reduced antioxidant gene expression. These alterations might associate with MFN2/MAPK/AKT pathways. These findings broadened our understanding of airway remodeling and ASMC proliferation, which might provide a novel therapeutic target for asthma patients.

scholarly journals PK/PD Modeling of the PDE7 Inhibitor—GRMS-55 in a Mouse Model of Autoimmune Hepatitis

Pharmaceutics ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 597
Author(s):  
Artur Świerczek ◽  
Hanna Plutecka ◽  
Marietta Ślusarczyk ◽  
Grażyna Chłoń-Rzepa ◽  
Elżbieta Wyska
Keyword(s):  
Mouse Model ◽  
Autoimmune Hepatitis ◽  
Disease Progression ◽  
Hepatoprotective Activity ◽  
Mechanisms Of Action ◽  
Progression Model ◽  
Adrenoceptor Agonist ◽  
Tnf Α ◽  
Disease Progression Model ◽  
Time Courses

This study aimed to assess the efficacy and explore the mechanisms of action of a potent phosphodiesterase (PDE)7A and a moderate PDE4B inhibitor GRMS-55 in a mouse model of autoimmune hepatitis (AIH). The concentrations of GRMS-55 and relevant biomarkers were measured in the serum of BALB/c mice with concanavalin A (ConA)-induced hepatitis administered with GRMS-55 at two dose levels. A semi-mechanistic PK/PD/disease progression model describing the time courses of measured biomarkers was developed. The emetogenicity as a potential side effect of the studied compound was evaluated in the α2-adrenoceptor agonist-induced anesthesia model. The results indicate that liver damage observed in mice challenged with ConA was mainly mediated by TNF-α and IFN-γ. GRMS-55 decreased the levels of pro-inflammatory mediators and the transaminase activities in the serum of mice with AIH. The anti-inflammatory properties of GRMS-55, resulting mainly from PDE7A inhibition, led to a high hepatoprotective activity in mice with AIH, which was mediated by an inhibition of pro-inflammatory signaling. GRMS-55 did not induce the emetic-like behavior. The developed PK/PD/disease progression model may be used in future studies to assess the potency and explore the mechanisms of action of new investigational compounds for the treatment of AIH.

scholarly journals The protective role of Zingerone in a murine asthma model via activation of the AMPK/Nrf2/HO-1 pathway

2020 ◽  
Author(s):  
Yingjie Zhu ◽  
Jingjing Luo ◽  
You Xu ◽  
Shucheng Hua ◽  
Dan Li ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Active Compound ◽  
Protective Role ◽  
Asthma Model ◽  
Common Illnesses ◽  
Murine Asthma Model ◽  
Chronic Airway

Asthma is one of the most common illnesses associated with chronic airway inflammation; however, there are currently no effective therapies apart from glucocorticoids. Zingerone (ZIN), an active compound isolated from...

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