scholarly journals Protective Effects of Thalidomide on High-Glucose-Induced Podocyte Injury through In Vitro Modulation of Macrophage M1/M2 Differentiation

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Hui Liao ◽  
Yuanping Li ◽  
Xilan Zhang ◽  
Xiaoyun Zhao ◽  
Dan Zheng ◽  
...  
Keyword(s):  
High Glucose ◽  
Macrophage Polarization ◽  
Mannose Receptor ◽  
Raw 264.7 Cells ◽  
Protective Effects ◽  
Activated Macrophages ◽  
Podocyte Injury ◽  
Protein Expressions ◽  
Activated Macrophage

Objective. It has been shown that podocyte injury represents an important pathological basis that contributes to proteinuria and eventually leads to kidney failure. High glucose (HG) activates macrophage polarization, further exacerbating HG-induced podocyte injury. Our previous study on diabetic nephropathy rats indicated that thalidomide (Tha) has renoprotective properties. The present study explored the effects of Tha on mRNA and protein expressions of inducible nitric oxide synthase (iNOS), tumor necrosis factor- (TNF-) α, mannose receptor (CD206), and arginase- (Arg-) 1 in HG-activated macrophages. iNOS and TNF-α are established as markers of classically activated macrophage (M1). CD206 and Arg-1 are regarded as markers of alternatively activated macrophages (M2). During the experiment, the supernatants of (HG)-treated and (Tha)-treated macrophages, designated as (HG) MS and (Tha) MS, were simultaneously collected and processed. TNF-α and interleukin- (IL-) 1β levels as well as protein expressions of nephrin and podocin in HG, (HG) MS, and (Tha) MS-cultured podocytes were evaluated. The results showed that compared to the 11.1 mM normal glucose (NG), the 33.3 mM HG-cultured RAW 264.7 cells exhibited upregulated iNOS and TNF-α mRNAs and protein expressions, and downregulated CD206 and Arg-1 expressions significantly (p<0.05). Tha 200 μg/ml suppressed iNOS and TNF-α, and promoted CD206 and Arg-1 expressions significantly compared to the HG group (p<0.05). Furthermore, (HG) MS-treated podocytes showed an increase in TNF-α and IL-1β levels and a downregulation in nephrin and podocin expression significantly compared to NG-treated and HG-treated podocytes (p<0.05). The (Tha 200 μg/ml) MS group exhibited a decrease in TNF-α and IL-1β level, and an upregulation in nephrin and podocin expressions significantly compared to the (HG) MS group (p<0.05). Our research confirmed that HG-activated macrophage differentiation aggravates HG-induced podocyte injury in vitro and the protective effects of Tha might be related to its actions on TNF-α and IL-1β levels via its modulation on M1/M2 differentiation.

scholarly journals Protective Effects of Two Safflower Derived Compounds, Kaempferol and Hydroxysafflor Yellow A, on Hyperglycaemic Stress-Induced Podocyte Apoptosis via Modulating of Macrophage M1/M2 Polarization

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Yuanping Li ◽  
Dan Zheng ◽  
Dayue Shen ◽  
Xilan Zhang ◽  
Xiaoyun Zhao ◽  
...  
Keyword(s):  
Survival Rate ◽  
Macrophage Polarization ◽  
Mannose Receptor ◽  
M2 Macrophage ◽  
Protective Effects ◽  
Hydroxysafflor Yellow A ◽  
Real Time Quantitative Pcr ◽  
M2 Polarization ◽  
Oxide Synthase

Objective. The primary initiating mechanism in diabetes nephropathy (DN) is hyperglycemia-induced inflammation in which macrophage and podocyte play important roles. The present research is aimed at exploring the effects of kaempferol (Ka) and hydroxysafflor yellow A (HSYA) on classically activated (M1)/alternatively activated (M2) macrophage polarization and podocyte apoptosis under hyperglycaemic conditions in vitro. Methods. (1) RAW264.7 cells were treated with 11.1 mM glucose (NG), 33.3 mM glucose (HG), Ka 4–8 μM, and HSYA 100–200 μM separately. The expressions of inducible nitric oxide synthase (iNOS), tumor necrosis factor- (TNF-) α, mannose receptor (CD206), and arginase- (Arg-) 1 were quantified by Western blotting and real-time quantitative PCR. The collected supernatants from macrophage were named as (NG) MS, (HG) MS, (Ka) MS, and (HSYA) MS. (2) The podocyte survival rate was assessed by Bromodeoxyuridine assay, while TNF-α and interleukin- (IL-) 1β levels were evaluated by Elisa. Results. (1) Compared to the HG group, the Ka and HSYA 100 μM groups decreased iNOS and TNF-α levels and increased Arg-1 and CD206 expressions significantly (protein and mRNA: p<0.05, respectively). (2) The podocyte survival rate of Ka 8 μM was higher than that of HG, and the rates of (Ka) MS and (HSYA 100 μM) MS were higher than that of (HG) MS significantly (all: p<0.05). (3) TNF-α and IL-1β levels of Ka and HSYA 100 μM were significantly lower than those of the HG group, and both levels in the (Ka) MS and (HSYA) MS were lower than those in the (HG) MS group significantly (p<0.05, respectively). Conclusion. The protective effects of Ka and HSYA on podocyte apoptosis under hyperglycemic stress are related to their modulation on M1/M2 polarization and the lowering effects on TNF-α and IL-1β levels.

scholarly journals Increased long noncoding RNA maternally expressed gene 3 contributes to podocyte injury induced by high glucose through regulation of mitochondrial fission

2020 ◽  
Vol 11 (9) ◽  
Author(s):  
Qiongxia Deng ◽  
Ruowei Wen ◽  
Sirui Liu ◽  
Xiaoqiu Chen ◽  
Shicong Song ◽  
...  
Keyword(s):  
High Glucose ◽  
Noncoding Rna ◽  
Diabetic Kidney Disease ◽  
Mitochondrial Fission ◽  
Diabetic Mice ◽  
Podocyte Injury ◽  
Mitochondrial Translocation ◽  
Maternally Expressed Gene 3

Abstract Excessive mitochondrial fission plays a key role in podocyte injury in diabetic kidney disease (DKD), and long noncoding RNAs (lncRNAs) are important in the development and progression of DKD. However, lncRNA regulation of mitochondrial fission in podocytes is poorly understood. Here, we studied lncRNA maternally expressed gene 3 (Meg3) in mitochondrial fission in vivo and in vitro using human podocytes and Meg3 podocyte-specific knockdown mice. Expression of lncRNA Meg3 in STZ-induced diabetic mice was higher, and correlated with the number of podocytes. Excessive mitochondrial fission of podocytes and renal histopathological and physiological parameters were improved in podocyte-specific Meg3 knockdown diabetic mice. Elongated mitochondria with attenuated podocyte damage, as well as mitochondrial translocation of dynamin-related protein 1 (Drp1), were decreased in Meg3 knockout podocytes. By contrast, increased fragmented mitochondria, podocyte injury, and Drp1 expression and phosphorylation were observed in lncRNA Meg3-overexpressing podocytes. Treatment with Mdivi1 significantly blunted more fragmented mitochondria and reduced podocyte injury in lncRNA Meg3-overexpressing podocytes. Finally, fragmented mitochondria and Drp1 mitochondrial translocation induced by high glucose were reduced following treatment with Mdivi1. Our data show that expression of Meg3 in podocytes in both human cells and diabetic mice was higher, which regulates mitochondrial fission and contributes to podocyte injury through increased Drp1 and its translocation to mitochondria.

scholarly journals Fargesin ameliorates osteoarthritis via macrophage reprogramming by downregulating MAPK and NF-κB pathways

2020 ◽  
Author(s):  
Jiansen Lu ◽  
Hongbo Zhang ◽  
Jianying Pan ◽  
Zhiqiang Hu ◽  
Liangliang Liu ◽  
...  
Keyword(s):  
Macrophage Polarization ◽  
In Vitro Study ◽  
Cartilage Degeneration ◽  
Research Society ◽  
Preventive Strategy ◽  
Protective Effects ◽  
Erk Mapk ◽  
M1 Macrophage ◽  
Main Components

Abstract Synovial macrophage polarization and interactions between chondrocytes and macrophages are essential for osteoarthritis (OA) development. The present study determined the role and regulatory mechanisms of fargesin, one of the main components of Magnolia fargesii, in macrophage reprogramming and crosstalk across cartilage and synovium. 10-week-old male C57BL/6 mice were randomly assigned to sham-operated, collagenase-induced OA (CIOA)-operated, or CIOA-operated with intraarticular fargesin treatment groups. Fargesin attenuated articular cartilage degeneration and synovitis, resulting in substantially lower Osteoarthritis Research Society International (OARSI) and synovitis scores. In particular, significantly increased M2 polarization and decreased M1 polarization in synovial macrophages were found in fargesin-treated CIOA mice compared to controls. This was accompanied by down-regulation of IL-6 and IL-1β and upregulation of IL-10 in serum. Although conditioned medium (CM) from the M1 macrophage treated with fargesin reduced the expression of matrix metalloproteinase-13, RUNX2, and type X collagen X in OA cartilage, it had no direct effect on chondrocyte metabolism in an in vitro study. Moreover, fargesin exerted protective effects by suppressing p38/ERK MAPK and p65/NF-κB signaling. This study showed that fargesin switched the polarized phenotypes of macrophages from M1 to M2 subtypes and prevented cartilage degeneration partially by down-regulating p38/ERK MAPK and p65/NF-κB signaling. Targeting macrophage reprogramming or blocking the crosstalk between macrophages and chondrocytes in early OA may be an effective preventive strategy.

scholarly journals Tetrahydrocurcumin Ameliorates Diabetic Cardiomyopathy by Attenuating High Glucose-Induced Oxidative Stress and Fibrosis via Activating the SIRT1 Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Kaifeng Li ◽  
Mengen Zhai ◽  
Liqing Jiang ◽  
Fan Song ◽  
Bin Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathway ◽  
Diabetic Cardiomyopathy ◽  
High Glucose ◽  
Therapeutic Potential ◽  
Ros Generation ◽  
Protective Effects ◽  
Collagen Iii

Hyperglycemia-induced oxidative stress and fibrosis play a crucial role in the development of diabetic cardiomyopathy (DCM). Tetrahydrocurcumin (THC), a major bioactive metabolite of natural antioxidant curcumin, is reported to exert even more effective antioxidative and superior antifibrotic properties as well as anti-inflammatory and antidiabetic abilities. This study was designed to investigate the potential protective effects of THC on experimental DCM and its underlying mechanisms, pointing to the role of high glucose-induced oxidative stress and interrelated fibrosis. In STZ-induced diabetic mice, oral administration of THC (120 mg/kg/d) for 12 weeks significantly improved the cardiac function and ameliorated myocardial fibrosis and cardiac hypertrophy, accompanied by reduced reactive oxygen species (ROS) generation. Mechanically, THC administration remarkably increased the expression of the SIRT1 signaling pathway both in vitro and in vivo, further evidenced by decreased downstream molecule Ac-SOD2 and enhanced deacetylated production SOD2, which finally strengthened antioxidative stress capacity proven by repaired activities of SOD and GSH-Px and reduced MDA production. Additionally, THC treatment accomplished its antifibrotic effect by depressing the ROS-induced TGFβ1/Smad3 signaling pathway followed by reduced expression of cardiac fibrotic markers α-SMA, collagen I, and collagen III. Collectively, these finds demonstrated the therapeutic potential of THC treatment to alleviate DCM mainly by attenuating hyperglycemia-induced oxidative stress and fibrosis via activating the SIRT1 pathway.

scholarly journals Alleviation by Mahuang Fuzi and Shenzhuo Decoction in High Glucose-Induced Podocyte Injury by Inhibiting the Activation of Wnt/β-Catenin Signaling Pathway, Resulting in Activation of Podocyte Autophagy

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Haoran Dai ◽  
Fei Liu ◽  
Xinping Qiu ◽  
Wenbin Liu ◽  
Zhaocheng Dong ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
High Glucose ◽  
Protective Mechanism ◽  
Podocyte Injury ◽  
Common Endpoint ◽  
Protein Expressions ◽  
Related Proteins ◽  
The Relationship ◽  
Excessive Activation ◽  
Organ Fibrosis

Background. Organ fibrosis is a common endpoint of a variety of diseases. Many studies have shown that the pathogenesis of diabetic kidney disease (DKD) is related to the excessive activation of the Wnt/β-catenin signaling pathway on podocytes, so the treatment of DKD starts from this signaling pathway. At the same time, DKD, as a metabolic disease, has many connections related to podocyte autophagy. Objectives. We experimented the effects of Mahuang Fuzi and Shenzhuo decoction (MFSD) which is the combination of Mahuang Fuzi decoction and Shenzhuo decoction in traditional Chinese medicine compounds used “The Golden Chamber” in high glucose-induced podocytes, determined whether this effect was related to Wnt/β-catenin signaling pathway, and further investigated the relationship between this effect and autophagy. Methods. The mice podocytes were stimulated by using 30 mmol/L of high glucose and serum containing MFSD or Wnt/β-catenin signaling pathway inhibitor DKK1 (100 ng/ml) was used to intervene podocytes before high glucose stimulation. Podocyte injury-related proteins, Wnt/β-catenin signaling pathway-related proteins, and autophagy-related proteins were detected by using western blotting and immunofluorescence analysis. Results. Our results showed that DKK1 and MFSD treatment significantly upregulated the protein expressions of nephrin, podocin, podocalyxin, and podoplanin in high glucose-induced podocytes and downregulated the β-catenin protein expression. Furthermore, the protein expressions of beclin1, LC3B, and P62 were also significantly increased in high glucose-induced podocytes. Conclusion. Our experiments confirmed that the destruction of podocytes in DKD is related to the excessive activation of Wnt/β-catenin signaling pathway and the inhibition of autophagy after activation. MFSD treatment can inhibit the activation of Wnt/β-catenin signaling pathway in podocytes stimulated by high glucose and helpful in reducing the podocyte injury. This protective mechanism can be related to the enhancement of podocyte autophagy by MFSD treatment.

scholarly journals Rapamycin and FTY720 Alleviate Atherosclerosis by Cross Talk of Macrophage Polarization and Autophagy

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Rui-zhen Sun ◽  
Ying Fan ◽  
Xiao Liang ◽  
Tian-tian Gong ◽  
Qi Wang ◽  
...  
Keyword(s):  
Lipid Accumulation ◽  
Macrophage Polarization ◽  
Foam Cells ◽  
Peritoneal Macrophages ◽  
Macrophage Phenotype ◽  
Activated Macrophages ◽  
Activated Macrophage ◽  
Phenotype Markers ◽  
Alternatively Activated ◽  
Classically Activated

Foam cell formation and macrophage polarization are involved in the pathologic development of atherosclerosis, one of the most important human diseases affecting large and medium artery walls. This study was designed to assess the effects of rapamycin and FTY720 (fingolimod) on macrophages and foam cells. Mouse peritoneal macrophages were collected and treated with rapamycin and FTY720 to study autophagy, polarization, and lipid accumulation. Next, foam cells were formed by oxidizing low-density lipoprotein to observe changes in lipid accumulation, autophagy, and polarization in rapamycin-treated or FTY720-treated foam cells. Lastly, foam cells that had been treated with rapamycin and FTY720 were evaluated for sphingosine 1-phosphate receptor (S1prs) expression. Autophagy microtubule-associated protein 1 light chain 3- (LC3-) II was increased, and classically activated macrophage phenotype markers interleukin- (IL-) 6, cyclooxygenase-2 (COX2), and inducible nitric oxide synthase (iNOS) were increased, whereas alternatively activated macrophage phenotype markers transforming growth factor- (TGF-)β, arginase 1 (Arg1), and mannose receptor C-type 1 (Mrc1) were decreased by rapamycin in peritoneal macrophages. LC3-II was also obviously enhanced, though polarization markers were unchanged in rapamycin-treated foam cells. Moreover, lipid accumulation was inhibited in rapamycin-treated macrophage cells but was unchanged in rapamycin-treated foam cells. For FTY720, LC3-II did not change, whereas TGF-β, Arg1 and Mrc1 were augmented, and IL-6 was suppressed in macrophages. However, LC3-II was increased, and TGF-β, ARG1 and MRC1 were strikingly augmented, whereas IL-6, COX2 and iNOS could be suppressed in foam cells. Furthermore, lipid accumulation was alleviated in FTY720-treated foam cells. Additionally, S1pr1 was markedly decreased in foam cells (P< .05); S1pr2, S1pr3, S1pr4 and S1pr5 were unchanged in rapamycin-treated foam cells. In FTY720-treated foam cells, S1pr3 and S1pr4 were decreased, and S1pr1, S1pr2 and S1pr5 were unchanged. Therefore, we deduced that rapamycin stimulated classically activated macrophages and supressed early atherosclerosis. Rapamycin may also stabilize artery plaques by preventing apoptosis and S1PR1 in advanced atherosclerosis. FTY720 allowed transformation of foam cells into alternatively activated macrophages through the autophagy pathway to alleviate advanced atherosclerosis.

scholarly journals Progranulin attenuates liver fibrosis by downregulating the inflammatory response

2019 ◽  
Vol 10 (10) ◽  
Author(s):  
Wonbeak Yoo ◽  
Jaemin Lee ◽  
Kyung Hee Noh ◽  
Sangmin Lee ◽  
Dana Jung ◽  
...  
Keyword(s):  
Liver Disease ◽  
Liver Fibrosis ◽  
Cell Activation ◽  
Stellate Cell ◽  
Raw 264.7 Cells ◽  
Protective Effects ◽  
Deficient Diet ◽  
A Cell

Abstract Progranulin (PGRN) is a cysteine-rich secreted protein expressed in endothelial cells, immune cells, neurons, and adipocytes. It was first identified for its growth factor-like properties, being implicated in tissue remodeling, development, inflammation, and protein homeostasis. However, these findings are controversial, and the role of PGRN in liver disease remains unknown. In the current study, we examined the effect of PGRN in two different models of chronic liver disease, methionine‐choline‐deficient diet (MCD)-induced non-alcoholic steatohepatitis (NASH) and carbon tetrachloride (CCl4)-induced liver fibrosis. To induce long-term expression of PGRN, PGRN-expressing adenovirus was delivered via injection into the tibialis anterior. In the CCl4-induced fibrosis model, PGRN showed protective effects against hepatic injury, inflammation, and fibrosis via inhibition of nuclear transcription factor kappa B (NF-κB) phosphorylation. PGRN also decreased lipid accumulation and inhibited pro-inflammatory cytokine production and fibrosis in the MCD-induced NASH model. In vitro treatment of primary macrophages and Raw 264.7 cells with conditioned media from hepatocytes pre-treated with PGRN prior to stimulation with tumor necrosis factor (TNF)-α or palmitate decreased their expression of pro-inflammatory genes. Furthermore, PGRN suppressed inflammatory and fibrotic gene expression in a cell culture model of hepatocyte injury and primary stellate cell activation. These observations increase our understanding of the role of PGRN in liver injury and suggest PGRN delivery as a potential therapeutic strategy in chronic inflammatory liver disease.

scholarly journals Hyperoside Suppresses Renal Inflammation by Regulating Macrophage Polarization in Mice With Type 2 Diabetes Mellitus

2021 ◽  
Vol 12 ◽  
Author(s):  
Jialing Liu ◽  
Yanmei Zhang ◽  
Hongqin Sheng ◽  
Chunling Liang ◽  
Huazhen Liu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cell ◽  
Macrophage Polarization ◽  
Fasting Blood Glucose ◽  
Therapeutic Effects ◽  
Protective Effects ◽  
Monocyte Chemoattractant Protein 1 ◽  
Anti Inflammatory

Accumulating evidence reveals that both inflammation and lymphocyte dysfunction play a vital role in the development of diabetic nephropathy (DN). Hyperoside (HPS) or quercetin-3-O-galactoside is an active flavonoid glycoside mainly found in the Chinese herbal medicine Tu-Si-Zi. Although HPS has a variety of pharmacological effects, including anti-oxidative and anti-apoptotic activities as well as podocyte-protective effects, its underlying anti-inflammatory mechanisms remain unclear. Herein, we investigated the therapeutic effects of HPS on murine DN and the potential mechanisms responsible for its efficacy. We used C57BLKS/6J Lepdb/db mice and a high glucose (HG)-induced bone marrow-derived macrophage (BMDM) polarization system to investigate the potentially protective effects of HPS on DN. Our results showed that HPS markedly reduced diabetes-induced albuminuria and glomerular mesangial matrix expansion, accompanied with a significant improvement of fasting blood glucose level, hyperlipidaemia and body weight. Mechanistically, pretreatment with HPS effectively regulated macrophage polarization by shifting proinflammatory M1 macrophages (F4/80+CD11b+CD86+) to anti-inflammatory M2 ones (F4/80+CD11b+CD206+) in vivo and in bone marrow-derived macrophages (BMDMs) in vitro, resulting in the inhibition of renal proinflammatory macrophage infiltration and the reduction in expression of monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor (TNF-α) and inducible nitric oxide synthase (iNOS) while increasing expression of anti-inflammatory cytokine Arg-1 and CD163/CD206 surface molecules. Unexpectedly, pretreatment with HPS suppressed CD4+ T cell proliferation in a coculture model of IL-4-induced M2 macrophages and splenic CD4+ T cells while promoting their differentiation into CD4+IL-4+ Th2 and CD4+Foxp3+ Treg cells. Taken together, we demonstrate that HPS ameliorates murine DN via promoting macrophage polarization from an M1 to M2 phenotype and CD4+ T cell differentiation into Th2 and Treg populations. Our findings may be implicated for the treatment of DN in clinic.

scholarly journals B cell activating factor regulates periodontitis development by suppressing inflammatory responses in macrophages

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Lixia Wang ◽  
Tianyi Zhang ◽  
Zheng Zhang ◽  
Zihan Wang ◽  
Yu-Jie Zhou ◽  
...  
Keyword(s):  
B Cell ◽  
Alveolar Bone ◽  
Macrophage Polarization ◽  
Raw 264.7 Cells ◽  
Raw 264.7 ◽  
Rt Pcr ◽  
B Cell Activating Factor ◽  
Tnf Α

Abstract Background B cell activating factor (BAFF) is a member of the tumor necrosis factor (TNF) superfamily with immunomodulatory effects on both innate and adaptive immune responses. Periodontitis is an inflammatory disease characterized by periodontal soft tissue inflammation and the progressive loss of periodontal ligament and alveolar bone. Macrophages are closely related to periodontitis progression. However, the role of BAFF in periodontitis development and macrophage polarization and the underlying mechanism remain unknown. Methods In vivo, a ligation-induced mouse model of periodontitis for BAFF blockade was established to investigate the expression of inducible nitric oxide synthase (iNOS) through real-time PCR (RT-PCR) and immunohistochemistry. In addition, the level of TNF-α in the periodontium, the number of osteoclasts, and alveolar bone resorption were observed. In vitro, RAW 264.7 macrophage cells were treated with 100 ng/mL Porphyromonas gingivalis lipopolysaccharide (P. gingivalis LPS) in either the presence or absence of 50 nM small interfering RNA (siRNA) targeting BAFF, followed by further incubation for 24 h. These cells and supernatants were collected and stored for RT-PCR, enzyme-linked immunosorbent assay, western blotting and immunofluorescence microscopy. Results In vivo, BAFF blockade decreased the levels of TNF-α in the periodontium in a ligature-induced mouse periodontitis model. Reduced osteoclast formation and lower alveolar bone loss were also observed. In addition, BAFF blockade was related to the expression of polarization signature molecules in macrophages. In vitro, BAFF knockdown notably suppressed the production of TNF-α in RAW 264.7 cells stimulated by P. gingivalis LPS. Moreover, BAFF knockdown attenuated the polarization of RAW 264.7 cells into classically activated macrophages (M1), with reduced expression of iNOS. Conclusions Based on our limited evidence, we showed BAFF blockade exhibits potent anti-inflammatory properties in mice experimental periodontitis in vivo and in P. gingivalis LPS-treated RAW 264.7 cells in vitro, and macrophage polarization may be responsible for this effect.

scholarly journals Glycoproteins From Rabdosia japonica var. glaucocalyx Regulate Macrophage Polarization and Alleviate Lipopolysaccharide-Induced Acute Lung Injury in Mice via TLR4/NF-κB Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
An-qi Ren ◽  
Hui-jun Wang ◽  
Hai-yan Zhu ◽  
Guan Ye ◽  
Kun Li ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Western Blot ◽  
Mononuclear Cells ◽  
Macrophage Polarization ◽  
Enzyme Linked Immunosorbent Assay ◽  
Protective Effects ◽  
Proinflammatory Mediators ◽  
Tnf Α

Background and Aims:Rabdosia japonica var. glaucocalyx is a traditional Chinese medicine (TCM) for various inflammatory diseases. This present work aimed to investigate the protective effects of R. japonica var. glaucocalyx glycoproteins on lipopolysaccharide (LPS)-induced acute lung injury (ALI) and the potential mechanism.Methods: Glycoproteins (XPS) were isolated from R. japonica var. glaucocalyx, and homogeneous glycoprotein (XPS5-1) was purified from XPS. ANA-1 cells were used to observe the effect of glycoproteins on the secretion of inflammatory mediators by enzyme-linked immunosorbent assay (ELISA). Flow cytometry assay, immunofluorescence assay, and Western blot analysis were performed to detect macrophage polarization in vitro. The ALI model was induced by LPS via intratracheal instillation, and XPS (20, 40, and 80 mg/kg) was administered intragastrically 2 h later. The mechanisms of XPS against ALI were investigated by Western blot, ELISA, and immunohistochemistry.Results:In vitro, XPS and XPS5-1 downregulated LPS-induced proinflammatory mediators production including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, and nitric oxide (NO) and upregulated LPS-induced IL-10 secretion. The LPS-stimulated macrophage polarization was also modulated from M1 to M2. In vivo, XPS maintained pulmonary histology with significantly reducing protein concentration and numbers of mononuclear cells in bronchoalveolar lavage fluid (BALF). The level of IL-10 in BALF was upregulated by XPS treatment. The level of cytokines including TNF-α, IL-1β, and IL-6 was downregulated. XPS also decreased infiltration of macrophages and polymorphonuclear leukocytes (PMNs) in lung. XPS suppressed the expression of key proteins in the TLR4/NF-κB signal pathway.Conclusion: XPS was demonstrated to be a potential agent for treating ALI. Our findings might provide evidence supporting the traditional application of R. japonica var. glaucocalyx in inflammation-linked diseases.

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