scholarly journals Lipocalin 2 is a Regulator Of Macrophage Polarization and NF-κB/STAT3 Pathway Activation

2014 ◽  
Vol 28 (10) ◽  
pp. 1616-1628 ◽  
Author(s):  
Hong Guo ◽  
Daozhong Jin ◽  
Xiaoli Chen
Keyword(s):  
Time Course ◽  
Target Genes ◽  
Macrophage Polarization ◽  
Lipocalin 2 ◽  
Regulation Of Expression ◽  
Arginase 1 ◽  
Pathway Activation ◽  
M1 Macrophage ◽  
Stat3 Phosphorylation ◽  
Pre Treatment

Lipocalin 2 (Lcn2) has been previously characterized as an adipokine/cytokine and implicated in obesity and inflammation. Herein, we investigated the role and potential mechanism of Lcn2 in the regulation of macrophage polarization in obesity-associated inflammation. We observed that Lcn2−/− mice displayed an up-regulation of expression of M1 macrophage marker Cd11c but a down-regulation of M2 marker arginase 1 in adipose tissue and liver of mice upon a high-fat diet feeding. Lcn2-deficient bone marrow–derived macrophages (BMDMs) were more sensitive to lipopolysaccharide (LPS) stimulation, leading to a more profound up-regulation of expression of pro-inflammatory markers than wild-type (WT) BMDMs. Accordingly, LPS stimulation elicited an increase in the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), c-Jun, and STAT3 signaling pathways as well as an up-regualtion of expression of NF-κB and STAT3 target genes such as IL-1β, IL-6, iNOS, and MCP-1 in Lcn2−/− BMDMs compared with WT controls. Pre-treatment of recombinant Lcn2 attenuated LPS-stimulated degradation of IκBα and STAT3 phosphorylation as well as LPS-induced gene expression of IL-6 and iNOS in Lcn2−/− BMDMs. Moreover, the NFκB inhibitor markedly blocked LPS-stimulated STAT3 phosphorylation in Lcn2−/− BMDMs. These results together with the time course of Lcn2 secretion, NFκB and STAT3 phosphorylation in response to LPS stimulation, suggest that Lcn2 plays a role as an anti-inflammatory regulator in macrophage activation via modulating a feed-forward activation of NFκB-STAT3 loop.

scholarly journals ECM1 is an essential factor for the determination of M1 macrophage polarization in IBD in response to LPS stimulation

2020 ◽  
Vol 117 (6) ◽  
pp. 3083-3092 ◽  
Author(s):  
Yaguang Zhang ◽  
Xuezhen Li ◽  
Zhongguang Luo ◽  
Liyan Ma ◽  
Songling Zhu ◽  
...  
Keyword(s):  
Matrix Protein ◽  
Intestinal Inflammation ◽  
Macrophage Polarization ◽  
Extracellular Matrix Protein ◽  
Mechanistic Study ◽  
Macrophage Phenotype ◽  
Inflammatory Conditions ◽  
Arginase 1 ◽  
M1 Macrophage ◽  
Macrophage Colony

Inflammatory bowel disease (IBD) comprises chronic relapsing disorders of the gastrointestinal tract characterized pathologically by intestinal inflammation and epithelial injury. Here, we uncover a function of extracellular matrix protein 1 (ECM1) in promoting the pathogenesis of human and mouse IBD. ECM1 was highly expressed in macrophages, particularly tissue-infiltrated macrophages under inflammatory conditions, and ECM1 expression was significantly induced during IBD progression. The macrophage-specific knockout of ECM1 resulted in increased arginase 1 (ARG1) expression and impaired polarization into the M1 macrophage phenotype after lipopolysaccharide (LPS) treatment. A mechanistic study showed that ECM1 can regulate M1 macrophage polarization through the granulocyte-macrophage colony-stimulating factor/STAT5 signaling pathway. Pathological changes in mice with dextran sodium sulfate-induced IBD were alleviated by the specific knockout of the ECM1 gene in macrophages. Taken together, our findings show that ECM1 has an important function in promoting M1 macrophage polarization, which is critical for controlling inflammation and tissue repair in the intestine.

scholarly journals The USP14–NLRC5 pathway inhibits titanium particle–induced osteolysis in mice by suppressing NF-κB and PI3K/AKT activities

2020 ◽  
Vol 295 (20) ◽  
pp. 7018-7032 ◽  
Author(s):  
Guibin Fang ◽  
Yuan Fu ◽  
Shixun Li ◽  
Junxiong Qiu ◽  
Manyuan Kuang ◽  
...  
Keyword(s):  
Macrophage Polarization ◽  
Wear Particle ◽  
Wear Particles ◽  
Titanium Particle ◽  
Pathway Activation ◽  
M1 Macrophage ◽  
Phosphoinositide 3 Kinase ◽  
Factor Α

Total hip arthroplasty (THA) is a widely-used surgical intervention for treating patients with end-stage degenerative and inflammatory osteoarthropathy. However, wear particles from the artificial titanium joint can induce osteolysis, limiting the long-term survivorship of THA. Monocyte/macrophage lineage cells are the key players in the response to wear particles, and the proinflammatory NF-κB and phosphoinositide 3-kinase (PI3K)–AKT Ser/Thr kinase (AKT)-signaling pathways have been shown to be the most important contributors to wear particle–induced osteolysis. In contrast, ubiquitin-specific protease 14 (USP14) specifically removes the polyubiquitin chains from the nucleotide-binding and oligomerization domain (NOD)-like receptor family Caspase recruitment domain (CARD)–containing 5 (NLRC5) and thereby enhances the NLRC5-mediated inhibition of NF-κB signaling. In this study, we aimed to clarify the role of the USP14–NLRC5 pathway in wear particle–induced osteolysis in vitro and in vivo. We found that NLRC5 or USP14 overexpression inhibits titanium particle–induced proinflammatory tumor necrosis factor α (TNFα) production and NF-κB pathway activation, and it also decreases M1 macrophage polarization and PI3K/AKT pathway activation. Of note, NLRC5 and USP14 overexpression attenuated titanium particle–induced cranial osteolysis in mice. In conclusion, the findings of our study indicate that the USP14–NLRC5 pathway inhibits titanium particle–induced osteolysis by suppressing the NF-κB and PI3K/AKT pathways both in vitro and in vivo.

scholarly journals Sarcodia suieae acetyl-xylogalactan regulate RAW 264.7 macrophage NF-kappa B activation and IL-1 beta cytokine production in macrophage polarization

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Tsung-Meng Wu ◽  
Fan-Hua Nan ◽  
Kuan-Chu Chen ◽  
Yu-Sheng Wu
Keyword(s):  
Target Genes ◽  
Cytokine Production ◽  
Quantitative Polymerase Chain Reaction ◽  
Macrophage Polarization ◽  
Cell Counting ◽  
Raw 264.7 ◽  
Sequencing Analysis ◽  
Macrophage Polarisation ◽  
Raw 264.7 Macrophage ◽  
M1 Macrophage

AbstractIn this study, the effects of acetyl-xylogalactan extracted from Sarcodia suieae on RAW 264.7 macrophage polarisation were evaluated. This extracted acetyl-xylogalactan had a monosaccharide composition of 91% galactose and 9% xylose, with polysaccharide and acetyl contents of 80.6% and 19.3%, respectively. MALDI–TOF mass spectrometry and NMR spectroscopy revealed the molecular weight of the acetyl-xylogalactan to be 88.5 kDa. After acetyl-xylogalactan treatment, RAW 264.7 macrophage polarisation was noted, along with enhanced phagocytic ability. Furthermore, the Cell Counting Kit-8 (CCK-8) assay was performed and the results demonstrated non-significant alteration in lactate dehydrogenase levels in the treated cells. Next, interleukin (IL) 1β, TNF, and Malt-1 expression in RAW 264.7 macrophages treated with the S. suieae acetyl-xylogalactan was investigated through real-time quantitative polymerase chain reaction, and the results demonstrated that S. suieae acetyl-xylogalactan induced IL-1β and Malt-1 expression. RNA sequencing analysis results indicated the S. suieae acetyl-xylogalactan positively regulated cytokine production and secretion, protein secretion, and response to IL-1 activation, based on the observed GO terms. The predicted target genes in the GO enrichment analysis were found to upregulate NF-κB signalling and M0 to M1 macrophage conversion through the observed cytokine production. Thus, acetyl-xylogalactan can positively regulate RAW 264.7 macrophage polarisation.

scholarly journals Lipopolysaccharide-Enhanced Responses against Aryl Hydrocarbon Receptor in FcgRIIb-Deficient Macrophages, a Profound Impact of an Environmental Toxin on a Lupus-Like Mouse Model

2021 ◽  
Vol 22 (8) ◽  
pp. 4199
Author(s):  
Kanyarat Udompornpitak ◽  
Thansita Bhunyakarnjanarat ◽  
Awirut Charoensappakit ◽  
Cong Phi Dang ◽  
Wilasinee Saisorn ◽  
...  
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Inflammatory Responses ◽  
Macrophage Polarization ◽  
Environmental Pollutants ◽  
Annexin V ◽  
Aryl Hydrocarbon ◽  
Gamma Receptor ◽  
M1 Macrophage ◽  
Environmental Toxin ◽  
Pre Treatment

Fc gamma receptor IIb (FcgRIIb) is the only inhibitory-FcgR in the FcgR family, and FcgRIIb-deficient (FcgRIIb−/−) mice develop a lupus-like condition with hyper-responsiveness against several stimulations. The activation of aryl hydrocarbon receptor (Ahr), a cellular environmental sensor, might aggravate activity of the lupus-like condition. As such, 1,4-chrysenequinone (1,4-CQ), an Ahr-activator, alone did not induce supernatant cytokines from macrophages, while the 24 h pre-treatment by lipopolysaccharide (LPS), a representative inflammatory activator, prior to 1,4-CQ activation (LPS/1,4-CQ) predominantly induced macrophage pro-inflammatory responses. Additionally, the responses from FcgRIIb−/− macrophages were more prominent than wild-type (WT) cells as determined by (i) supernatant cytokines (TNF-α, IL-6, and IL-10), (ii) expression of the inflammation associated genes (NF-κB, aryl hydrocarbon receptor, iNOS, IL-1β and activating-FcgRIV) and cell-surface CD-86 (a biomarker of M1 macrophage polarization), and (iii) cell apoptosis (Annexin V), with the lower inhibitory-FcgRIIb expression. Moreover, 8-week-administration of 1,4-CQ in 8 week old FcgRIIb−/− mice, a genetic-prone lupus-like model, enhanced lupus characteristics as indicated by anti-dsDNA, serum creatinine, proteinuria, endotoxemia, gut-leakage (FITC-dextran), and glomerular immunoglobulin deposition. In conclusion, an Ahr activation worsened the disease severity in FcgRIIb−/− mice possibly through the enhanced inflammatory responses. The deficiency of inhibitory-FcgRIIb in these mice, at least in part, prominently enhanced the pro-inflammatory responses. Our data suggest that patients with lupus might be more vulnerable to environmental pollutants.

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