scholarly journals Danggui Buxue Tang Ameliorates Bleomycin-Induced Pulmonary Fibrosis by Suppressing the TLR4/NLRP3 Signaling Pathway in Rats

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Jiepeng Wang ◽  
Hao Wang ◽  
Fang Fang ◽  
Chaoyi Fang ◽  
Shaoxian Wang ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Signaling Pathway ◽  
Smooth Muscle Actin ◽  
Interleukin 1 ◽  
Sprague Dawley ◽  
Alpha Smooth Muscle Actin ◽  
Potent Effect ◽  
Necrosis Factor Alpha ◽  
Danggui Buxue Tang ◽  
Collagen Iii

Objective. To investigate the effects of Danggui Buxue Tang (DBT) on rats with pulmonary fibrosis (PF) and the underlying mechanism. Methods. Sixty specific pathogen-free (SPF) male Sprague-Dawley (SD) rats were randomly divided into 4 groups: control, PF, prednisone treatment, and DBT treatment. Intratracheal instillation of bleomycin (BLM) was performed to establish a PF rat model. DBT was administered to PF rats concurrently for 2 weeks. Lung samples were then collected for HE and Masson staining after pulmonary function testing, and semiquantitative analysis for the degree of alveolitis and fibrosis was performed using the Szapiel and Ashcroft score systems. Myeloperoxidase (MPO) activity, hydroxyproline (HYP), hyaluronic acid (HA), and inflammatory cytokine content were measured. Western blotting was performed to detect fibrotic marker and TLR4/NLRP3 signaling pathway changes. Results. Oral administration of DBT attenuated weight loss, survival rate, and pulmonary index. Lung histopathologic lesions were also reduced. DBT inhibited PF by decreasing the secretion of inflammatory cytokines and collagen deposition. Specifically, DBT reduced tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL-1β), IL-6, HYP, alpha-smooth muscle actin (α-SMA), collagen I, and collagen III levels. Corollary experiments identified a potential mechanism involving suppression of TLR4/MyD88/NF-κB signaling pathway activation and the NLRP3/ASC/caspase-1 axis, the downstream regulatory pathway. Conclusion. DBT exhibited a potent effect on BLM-induced PF rats by inhibiting the TLR4/NLRP3 signaling pathway. Thus, DBT alleviates pulmonary inflammation to inhibit fibrotic pathology and should be considered as a candidate for the clinical treatment of PF.

scholarly journals Cells isolated from the human cortical interstitium resemble myofibroblasts and bind neutrophils in an ICAM-1--dependent manner.

1997 ◽  
Vol 8 (4) ◽  
pp. 604-615 ◽  
Author(s):  
A Clayton ◽  
R Steadman ◽  
J D Williams
Keyword(s):  
Smooth Muscle Actin ◽  
Interleukin 1 ◽  
Selection Marker ◽  
Specific Marker ◽  
Dependent Manner ◽  
Alpha Smooth Muscle Actin ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Inflammatory Infiltrates

Progressive renal disease is frequently accompanied by renal interstitial inflammation and fibrosis in which the activity of resident fibroblasts may be of central importance. Because there are relatively few fibroblasts in the normal cortical interstitium and there is no specific marker to permit their identification, these cells have proved difficult to characterize in vitro. In this study, these cells were isolated and established in culture, using CD90 as a positive selection marker. Antibodies to CD90 bound to tubular epithelial cells and fibroblasts, but not to glomerular cells in kidney sections. In culture, only fibroblasts were CD90-positive. These normal renal cortical fibroblasts (RCF) were alpha-smooth muscle actin- and vimentin-positive, but desmin-, cytokeratin-, and factor VIII-negative, identifying them as myofibroblasts. They expressed platelet-derived growth factor alpha and beta receptors; CD44; and alpha 2, beta 1, and beta 3 integrin chains: this combination of markers was also characteristic of fibroblasts in sections of normal cortex. These cells were positive for ICAM-1 but negative for VCAM-1. Similarly, proliferating or growth-arrested renal cortical fibroblasts (RCF) in culture expressed ICAM-1 but not VCAM-1. The expression of VCAM-1 was detected, however, and that of ICAM-1 was increased on fibroblasts associated with inflammatory infiltrates in sections from fibrotic kidneys, and ICAM-1 and VCAM-1 were up-regulated on RCF in culture after incubation with increasing doses of interleukin-1 beta or tumor necrosis factor alpha (maximum between 24 and 48 h). These adhesion molecules were functional, and neutrophils adhered to resting and cytokine-activated RCF. Binding was maximal between 24 and 48 h after cytokine treatment and was inhibited by anti-CD18 antibodies. ICAM-1 is the principal adhesion molecule controlling inflammatory cell infiltration of the interstitium. The study presented here suggests that cortical fibroblasts may be central to the control of this infiltration.

scholarly journals Role of Human Primary Renal Fibroblast in TGF-β1-Mediated Fibrosis-Mimicking Devices

2021 ◽  
Vol 22 (19) ◽  
pp. 10758
Author(s):  
Seong-Hye Hwang ◽  
Yun-Mi Lee ◽  
Yunyeong Choi ◽  
Hyung Eun Son ◽  
Ji Young Ryu ◽  
...  
Keyword(s):  
Growth Factor ◽  
Renal Fibrosis ◽  
Transforming Growth Factor ◽  
Umbilical Vein ◽  
Smooth Muscle Actin ◽  
Interleukin 1 ◽  
Alpha Smooth Muscle Actin ◽  
Necrosis Factor Alpha ◽  
Tgf Β1 ◽  
Inhibitor Treatment

Renal fibrosis is a progressive chronic kidney disease that ultimately leads to end-stage renal failure. Despite several approaches to combat renal fibrosis, an experimental model to evaluate currently available drugs is not ideal. We developed fibrosis-mimicking models using three-dimensional (3D) co-culture devices designed with three separate layers of tubule interstitium, namely, epithelial, fibroblastic, and endothelial layers. We introduced human renal proximal tubular epithelial cells (HK-2), human umbilical-vein endothelial cells, and patient-derived renal fibroblasts, and evaluated the effects of transforming growth factor-β (TGF-β) and TGF-β inhibitor treatment on this renal fibrosis model. The expression of the fibrosis marker alpha smooth muscle actin upon TGF-β1 treatment was augmented in monolayer-cultured HK-2 cells in a 3D disease model. In the vascular compartment of renal fibrosis models, the density of vessels was increased and decreased in the TGF-β-treated group and TGF-β-inhibitor treatment group, respectively. Multiplex ELISA using supernatants in the TGF-β-stimulating 3D models showed that pro-inflammatory cytokine and growth factor levels including interleukin-1 beta, tumor necrosis factor alpha, basic fibroblast growth factor, and TGF-β1, TGF-β2, and TGF-β3 were increased, which mimicked the fibrotic microenvironments of human kidneys. This study may enable the construction of a human renal fibrosis-mimicking device model beyond traditional culture experiments.

scholarly journals Artemisinin Ameliorates Osteoarthritis by Inhibiting the Wnt/β-Catenin Signaling Pathway

2018 ◽  
Vol 51 (6) ◽  
pp. 2575-2590 ◽  
Author(s):  
Gang Zhong ◽  
Ruiming Liang ◽  
Jun Yao ◽  
Jia Li ◽  
Tongmeng Jiang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Cruciate Ligament ◽  
Interleukin 1 ◽  
Cartilage Degradation ◽  
Chondrocyte Apoptosis ◽  
Enzyme Linked Immunosorbent Assay ◽  
Cell Viability Assay ◽  
Necrosis Factor Alpha ◽  
Anti Inflammatory

Background/Aims: Current drug therapies for osteoarthritis (OA) are not practical because of the cytotoxicity and severe side-effects associated with most of them. Artemisinin (ART), an antimalarial agent, is well known for its safety and selectivity to kill injured cells. Based on its anti-inflammatory activity and role in the inhibition of OA-associated Wnt/β-catenin signaling pathway, which is crucial in the pathogenesis of OA, we hypothesized that ART might have an effect on OA. Methods: The chondro-protective and antiarthritic effects of ART on interleukin-1-beta (IL-1β)-induced and OA patient-derived chondrocytes were investigated in vitro using cell viability assay, glycosaminoglycan secretion, immunofluorescence, quantitative reverse transcription-polymerase chain reaction, and western blotting. We also used OA model rats constructed by anterior cruciate ligament transection and medial meniscus resection (ACLT+MMx) in the joints to investigate the effects of ART on OA by gross observation, morphological staining, immunohistochemistry, and enzyme-linked immunosorbent assay. Results: ART exhibited potent anti-inflammatory effects by inhibiting the expression of proinflammatory chemokines and cytokines, including interleukin (IL)-1β, IL-6, tumor necrosis factor alpha, and matrix metallopeptidase-13. It also showed favorable chondro-protective effect as evidenced by enhanced cell proliferation and viability, increased glycosaminoglycan deposition, prevention of chondrocyte apoptosis, and degeneration of cartilage. Further, ART inhibited OA progression and cartilage degradation via the Wnt/β-catenin signaling pathway, suggesting that it might serve as a Wnt/β-catenin antagonist to reduce inflammation and prevent cartilage degradation. Conclusion: In conclusion, ART alleviates IL-1β-mediated inflammatory response and OA progression by regulating the Wnt/β-catenin signaling pathway. Thereby, it might be developed as a potential therapeutic agent for OA.

Interleukin-1 beta alters actin expression and inhibits contraction of rat thoracic aorta

1992 ◽  
Vol 262 (4) ◽  
pp. C828-C833 ◽  
Author(s):  
L. A. Trinkle ◽  
D. Beasley ◽  
R. S. Moreland
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Protein Content ◽  
Muscle Activation ◽  
Smooth Muscle Actin ◽  
Interleukin 1 ◽  
Contractile Protein ◽  
Interleukin 1 Beta ◽  
Alpha Smooth Muscle Actin ◽  
Mlc Phosphorylation

Previous studies have indicated that interleukin-1 beta (IL-1) inhibits contraction of rat aortas by activating nitric oxide production in vascular smooth muscle cells, with subsequent increases in guanosine 3',5'-cyclic monophosphate (cGMP). This study determined if the effect of IL-1 involves the primary regulatory event in smooth muscle activation, myosin light chain (MLC) phosphorylation. This study also examined whether IL-1 affects contractile protein content. IL-1 (20 ng/ml) significantly decreased stress in response to 0.1 microM phenylephrine with a concomitant decrease in MLC phosphorylation. Incubation with IL-1 for 3 h or longer decreased alpha-smooth muscle actin and increased gamma-actin isoform, with no change in beta-nonmuscle actin or myosin isozyme content. These results suggest that IL-1 inhibition of a vascular smooth muscle contraction may be due to a decrease in activator calcium, which may account for the resultant decrease in MLC phosphorylation. These results also indicate that IL-1 significantly affects contractile protein content, enhancing gamma-actin isoforms and decreasing the vascular smooth muscle specific alpha-isoactin.

scholarly journals A Clearance Period after Soluble Lead Nanoparticle Inhalation Did Not Ameliorate the Negative Effects on Target Tissues Due to Decreased Immune Response

2020 ◽  
Vol 21 (22) ◽  
pp. 8738
Author(s):  
Jana Dumková ◽  
Tereza Smutná ◽  
Lucie Vrlíková ◽  
Bohumil Dočekal ◽  
Daniela Kristeková ◽  
...  
Keyword(s):  
Transforming Growth Factor Beta ◽  
Inductively Coupled Plasma ◽  
Structural Changes ◽  
Transforming Growth Factor ◽  
Smooth Muscle Actin ◽  
Soluble Form ◽  
Specific Response ◽  
Alpha Smooth Muscle Actin ◽  
Necrosis Factor Alpha ◽  
Target Organs

The inhalation of metal (including lead) nanoparticles poses a real health issue to people and animals living in polluted and/or industrial areas. In this study, we exposed mice to lead(II) nitrate nanoparticles [Pb(NO3)2 NPs], which represent a highly soluble form of lead, by inhalation. We aimed to uncover the effects of their exposure on individual target organs and to reveal potential variability in the lead clearance. We examined (i) lead biodistribution in target organs using laser ablation and inductively coupled plasma mass spectrometry (LA-ICP-MS) and atomic absorption spectrometry (AAS), (ii) lead effect on histopathological changes and immune cells response in secondary target organs and (iii) the clearance ability of target organs. In the lungs and liver, Pb(NO3)2 NP inhalation induced serious structural changes and their damage was present even after a 5-week clearance period despite the lead having been almost completely eliminated from the tissues. The numbers of macrophages significantly decreased after 11-week Pb(NO3)2 NP inhalation; conversely, abundance of alpha-smooth muscle actin (α-SMA)-positive cells, which are responsible for augmented collagen production, increased in both tissues. Moreover, the expression of nuclear factor κB (NF-κB) and selected cytokines, such as tumor necrosis factor alpha (TNFα), transforming growth factor beta 1 (TGFβ1), interleukin 6(IL-6), IL-1α and IL-1β , displayed a tissue-specific response to lead exposure. In summary, diminished inflammatory response in tissues after Pb(NO3)2 NPs inhalation was associated with prolonged negative effect of lead on tissues, as demonstrated by sustained pathological changes in target organs, even after long clearance period.

Microstructural changes and immunohistological analysis of pro-inflammatory cytokines in spleens of lipopolysaccharide-induced rats

2018 ◽  
Author(s):  
Y. B. Zhong ◽  
X. L. Zhang ◽  
M. Y. Lv ◽  
X. F. Hu ◽  
Y. Li
Keyword(s):  
Inflammatory Cytokines ◽  
Optical Density ◽  
Normal Saline ◽  
Interleukin 1 ◽  
Saline Group ◽  
Control Group ◽  
Sprague Dawley ◽  
Necrosis Factor Alpha ◽  
Lymphoid Follicles ◽  
Pro Inflammatory Cytokines

This study investigated splenic status changes in weaned Sprague-Dawley rats induced by lipopolysaccharide. There were forty 26-day-old rats selected randomly and equally divided into two groups. The treatment group received daily single doses of lipopolysaccharide, and the control group was treated with normal saline. We conducted haematoxylin-eosin staining, immunohistochemical staining and semi-quantitative optical density analysis for both groups on the 29th, 32nd, 35th and 38th days after treatment. The results indicated that splenic marginal zone in the lipopolysaccharide group was thinner or disappeared compared to that of the saline group. However, the periarterial lymphoid sheath and the diameters of splenic lymphoid follicles appeared thicker and wider than those in the saline group (P less than 0.05). The expression of interleukin-1 beta, interleukin-6 and tumour necrosis factor alpha was mainly localized within the periarterial lymphoid sheath and splenic lymphoid follicles in the lipopolysaccharide treated rats. The integrated optical density and the average optical density in the lipopolysaccharide group were greater than those in the normal saline treated group (P less than 0.05). In conclusion, splenic immune function is probably strengthened by altering microstructures and releasing pro-inflammatory cytokines following lipopolysaccharide treatment.

scholarly journals Pharmacological and Molecular Evidence of Neuroprotective Curcumin Effects Against Biochemical and Behavioral Sequels Caused by Methamphetamine: Possible Function of CREB-BDNF Signaling Pathway

2021 ◽  
Author(s):  
Mina Gholami ◽  
◽  
Farzad Hozuri ◽  
Setayesh Abdolkarimi ◽  
Mahsa Mahmoudi ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Interleukin 1 ◽  
Male Rats ◽  
Molecular Evidence ◽  
Necrosis Factor Alpha ◽  
Multiple Parameters ◽  
Pathway Activation ◽  
Factor Alpha ◽  
Bdnf Signaling ◽  
Induced Apoptosis

The neuroprotective impact of curcumin and the role of CREB-BDNF signaling in this way was evaluated in methamphetamine (METH)-induced neurodegeneration in rats. Sixty adult male rats were randomly split into 6 groups. While normal saline and 10 mg / kg METH were administered intraperitoneally in Groups 1 and 2, Groups 3, 4, 5 and 6 received METH (10 mg/kg) and Curcumin (10, 20, 40 and 80 mg/kg respectively) simultaneously. Morris Water Maze (MWM), oxidative hippocampal, antioxidant, inflammatory, apoptotic, and CREB and BDNF were assessed. We've found that METH disturbs learning and memory. Concurrent curcumin therapy (40 and 80 mg / kg) decreased cognitive disturbance caused by METH. Multiple parameters, such as lipid peroxidation, oxidized form of glutathione (GSSG), interleukin 1 beta (IL-1β), tumor necrosis factor alpha (TNF-α) and Bax, increased by METH therapy, although the reduced type of glutathione (GSH), Bcl-2, P-CREB and BDNF concentrations in the hippocampus decreased. Different doses of curcumin adversely attenuated METH-induced apoptosis, oxidative stress and inflammation, but enhanced concentrations of P-CREB and BDNF. Curcumin-caused neuroprotection against METH-induced neurodegeneration is conducted by P-CREB / BDNF signaling pathway activation.

scholarly journals NADPH Oxidase Signaling Pathway Mediates Mesenchymal Stem Cell-Induced Inhibition of Hepatic Stellate Cell Activation

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Haowen Qiao ◽  
Yu Zhou ◽  
Xingping Qin ◽  
Jing Cheng ◽  
Yun He ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Liver Fibrosis ◽  
Nadph Oxidase ◽  
Signaling Pathway ◽  
Cell Activation ◽  
Stellate Cell ◽  
Smooth Muscle Actin ◽  
Alpha Smooth Muscle Actin

Background. Bone marrow-derived mesenchymal stem cells (BMSCs) have blossomed into an effective approach with great potential for the treatment of liver fibrosis. The aim of this study was to investigate the underlying antifibrosis mechanisms by which the BMSC inhibit activated hepatic stellate cells (HSCs) in vivo and in vitro. Methods. To study the effect of human bone marrow-derived mesenchymal stem cells (hBM-MSCs) on activated HSCs, we used HSCs and the coculture systems to evaluate the inhibition of activated HSCs from the aspects of the apoptosis of activated HSCs. In addition, activation of NADPH oxidase pathway and the changes in liver histopathology were tested by using the carbon tetrachloride- (CCl4-) induced liver fibrosis in mice. Results. Introduction of hBM-MSCs significantly inhibited the proliferation of activated HSCs by inducing the apoptosis process of activated HSCs. The effect of hBM-MSCs reduced the signaling pathway of NADPH oxidase in activated HSCs. Besides, the signaling pathway of NADPH oxidase mediated hBM-MSC upregulation of the expression of the peroxisome proliferator-activated receptor γ and downregulation of the expression of α1(I) collagen and alpha-smooth muscle actin (α-SMA) in activated HSCs. Moreover, the hBM-MSC-induced decrease in the signaling pathway of NADPH oxidase was accompanied by the decrease of the activated HSC number and liver fibrosis in a mouse model of CCl4-induced liver fibrosis. Conclusion. The hBM-MSCs act as a promising drug source against liver fibrosis development with respect to hepatopathy as a therapeutic target.

scholarly journals Cordyceps militarisImproves Chronic Kidney Disease by Affecting TLR4/NF-κB Redox Signaling Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-16 ◽  
Author(s):  
Tingli Sun ◽  
Wenpeng Dong ◽  
Guohong Jiang ◽  
Jingbo Yang ◽  
Jizhang Liu ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Signaling Pathway ◽  
Interleukin 1 ◽  
Serum Levels ◽  
Redox Signaling ◽  
Cordyceps Militaris ◽  
Preparative Hplc ◽  
Necrosis Factor Alpha ◽  
Main Component

Cordyceps militarismay show good promise in protecting against chronic kidney disease (CKD) but the molecular mechanism remains unclear. CKD risk is associated with the Toll-like receptor 4/nuclear factor-kappa B (TLR4/NF-κB) signaling pathway. Cordycepin is the main component ofCordyceps militarisand may affect the TLR4/NF-κB pathway. Cordycepin was prepared by preparative HPLC. CKD patients were assigned intoCordyceps militaris(COG, 100 mg daily) and placebo (CG) groups. Cordycepin activity was measured using human embryo kidney cells (HEK293T). Biochemical indices, the levels of TLR4, NF-κB, cyclooxygenase-2 (COX2), tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β), were measured by real-time qRT-PCR, or ELISA kits and or Western blot. After 3-month treatment, cordycepin reduced the levels of urinal protein, blood urea nitrogen (BUN), and creatinine by36.7%±8.6%,12.5%±3.2%, and18.3%±6.6%, respectively (P<0.05).Cordyceps militarisimproved lipid profile and redox capacity of CKD patients by reducing the serum levels of TG, TC, and LDL-C by12.8%±3.6%,15.7%±4.1%, and16.5%±4.4%and increasing the HDL-C level by10.1%±1.4%in the COG group when compared with the CG group, respectively (P<0.05). The serum levels of cystatin-C (Cys-C), myeloperoxidase (MPO), and malondialdehyde (MDA) were reduced by14.0%±3.8%,26.9%±12.3%, and19.7%±7.9%while nitric oxide (NO) and superoxide dismutase (SOD) were increased by12.5%±2.9%and25.3%±13.4%in the COG group when compared with the CG group, respectively (P<0.05). Cordycepin reduced the levels of TLR4, NF-κB, COX2, TNF-α, and IL-1βin HEK293T cells too (P<0.05). However, cordycepin could not affect the levels anymore if TLR4 was silenced.Cordyceps militarisprotected against CKD progression by affecting the TLR4/NF-κB lipid and redox signaling pathway via cordycepin.

Sign in / Sign up

Export Citation Format

Share Document