INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
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2022
·Vol. 24
·期 1
·320
·
IF 6.208
Xiaoyu Zhang,Yuan Gao,Zhuangzhuang Liu,Wenjing Li,Yuan Kang,Ximeng Li,Zhenlu Xu,Cheng Peng,Yun Qi
As a worldwide health issue, obesity is associated with the infiltration of monocytes/macrophages into the adipose tissue causing unresolved inflammation. Monocyte chemoattractant protein-1 (MCP-1) exerts a crucial effect on obesity-related monocytes/macrophages infiltration. Clinically, aspirin and salsalate are beneficial for the treatment of metabolic diseases in which adipose tissue inflammation plays an essential role. Herein, we investigated the effect and precise mechanism of their active metabolite salicylate on TNF-α-elevated MCP-1 in adipocytes. The results indicated that salicylate sodium (SAS) could lower the level of MCP-1 in TNF-α-stimulated adipocytes, which resulted from a previously unrecognized target phosphodiesterase (PDE), 3B (PDE3B), rather than its known targets IKKβ and AMPK. The SAS directly bound to the PDE3B to inactivate it, thus elevating the intracellular cAMP level and activating PKA. Subsequently, the expression of MKP-1 was increased, which led to the decrease in p-EKR and p-p38. Both PDE3B silencing and the pharmacological inhibition of cAMP/PKA compromised the suppressive effect of SAS on MCP-1. In addition to PDE3B, the PDE3A and PDE4B activity was also inhibited by SAS. Our findings identify a previously unrecognized pathway through which SAS is capable of attenuating the inflammation of adipocytes.Keywords:cAMP;MKP-1;p-ERK;p-p38;metaflammation
研究领域:
药理学
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免疫学
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代谢
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产品关联
DOI
PubMed
高影响因子
INFLAMMATION
·
2022
·Vol. 46
·期 2
·534-554
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IF 4.657
Tong He,Wang Li,Zhang Kefan,Shi Jing,Wu Yongshuai,Bao Yulong,Wang Changshan
Noninfectious liver injury, including the effects of chemical material, drugs and diet, is a major cause of liver diseases worldwide. In chemical and drugs-induced liver injury, innate inflammatory responses are mediated by extracellular danger signals. The S100 protein can act as danger signals, which can promote the migration and chemotaxis of immune cells, promote the release of various inflammatory cytokines, and regulate the body’s inflammatory and immune responses. However, the role of S100A6 in inflammatory response in chemical and drugs-induced sterile liver injury remains unclear. We constructed the model of sterile liver injury induced by carbon tetrachloride (CCl 4 )/Paracetamol (APAP) and performed RNA sequencing (RNA-seq) on the liver tissues after injury (days 2 and 5). We analyzed inflammatory protein secretion in the liver tissue supernatant by enzyme-linked immunosorbent assay (ELISA), determined the inflammation response by bioinformatic analysis during sterile liver injury, and assessed mononuclear/macrophage infiltration by immunohistochemistry and flow cytometry. Immunohistochemistry was used to analyze the location of S100A6. We conducted inflammatory factor expression analysis and molecular mechanistic studies in Kupffer cells (KCs) induced by S100A6 using quantitative reverse transcription-polymerase chain reaction (qRT-PCR), ELISA, and western blot in vitro experiments. We performed chemokine CCL2 expression analysis and molecular mechanism studies using the same method. We used a Transwell assay to show the infiltration of mononuclear/macrophage. We here observed that aggravated inflammatory response was shown in CCl 4 and APAP-administrated mice, as evidenced by enhanced production of inflammatory cytokines (TNF-α, IL-1β), and elevated mononuclear/macrophage infiltration and activation of immunity. The expression of S100A6 was significantly increased on day 2 after sterile liver injury, which is primarily produced by injured liver cells. Mechanistic studies established that S100A6 activates Kupffer cells (KCs) via the p -P38, p -JNK and P65 pathways to induce inflammation in vitro . Furthermore, TNF-α can stimulate liver cells via the p -P38 and p -JNK pathways to produce CCL2 and promote the infiltration of mononuclear/macrophage. In summary, we showed that S100A6 plays an important role in regulating inflammation, thus influencing sterile liver injury. Our findings provide novel evidence that S100A6 can as a danger signal that contributes to pro-inflammatory activation through p -P38 and p -JNK pathways in CCl 4 and APAP-induced sterile liver injury in mice. In addition, the inflammatory factor TNF-α induces a large amount of CCL2 production in normal liver cells surrounding the injured area through a paracrine action, which is chemotactic for blood mononuclear/macrophage infiltration. Graphical Abstract
研究领域:
免疫学
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肝病学
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分子生物学
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病理学
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DOI
PubMed
高影响因子
Food & Function
·
2021
·Vol. 13
·期 3
·1393-1407
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IF 5.396
Liuming Xie,Zhibing Huang,Hui Meng,Zhibing Fan,Xiaoyi Shi,Jianhua Xie
Manipulating the structures, physicochemical properties, and monosaccharide compositions of exopolysaccharides (EPS) isolated from microorganisms has been reported to enhance their biological activities. Hence, the aim of this work was to examine the effects of genistein addition during fermentation on the amount, physicochemical properties, and immunomodulatory activity of EPS secreted by M. purpureus. Results showed that genistein addition significantly increased M. purpureus biomass and EPS yield to 2.42 g L−1 and 6.08 g L−1, respectively, and affected the physicochemical properties and structures of EPS. Furthermore, EPS produced by genistein-treated M. purpureus (G-EMP) improved the immunomodulatory activity of RAW264.7 macrophages by increasing the secretion of nitric oxide and cytokines. Moreover, phospho-Jun N-terminal kinase (p-JNK), phospho-extracellular regulated protein kinase (p-ERK), phospho-p38 (p-p38) mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) phospho-p65 (p65) proteins were remarkably upregulated by G-EMP stimulation, blocking Toll-like receptor 4 (TLR4) that dramatically reduced the pinocytic and phagocytic capacities. Overall, these findings provide potential rationales for the application of genistein in improving the EPS yield of M. purpureus.
研究领域:
微生物学
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免疫学
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生物技术
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产品关联
DOI
PubMed
高影响因子
Current Medical Science
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2018
·Vol. 38
·期 5
·853-860
·
IF 0
Zhou Dan-ni,Li Sai-jiao,Ding Jin-li,Yin Tai-lang,Yang Jing,Ye Hong
The polycystic ovary syndrome (PCOS) model was established in rats and correlation between the expression of macrophage migration inhibitory factor (MIF) and cytokinesis with the MAPK signalling pathway in the rat ovary was measured. The PCOS model in rats was established by dehydroepiandrosterone (DHEA). Thirty sexually immature female Sprague-Dawley rats were randomly and equally assigned to three groups: control group, PCOS group, and PCOS with high-fat diet (HFD) group. Serum hormones were assayed by radioimmunoassay (RIA). The ovaries were immunohistochemically stained with MIF, and the expression of MIF, p-JNK and p-p38 was detected by Western blotting in ovaries. The serum testosterone level, LH concentration, LH/FSH ratio, fasting insulin level and HOMA IR index in the PCOS group (6.077±0.478, 13.809±1.701, 1.820±0.404, 10.83±1.123 and 1.8692±0.1096) and PCOS with HFD group (6.075±0.439, 14.075±1.927, 1.779±0.277, 10.20±1.377 and 1.7736±0.6851) were significantly higher than those in the control group (4.949±0.337, 2.458±0.509, 1.239±0.038, 9.53±0.548 and 1.5329±0.7363), but there was no significant difference between the PCOS group and PCOS with HFD group. The expression levels of MIF, p-JNK, and p-p38 in the PCOS group (0.4048±0.013, 0.6233±0.093 and 0.7987±0.061) and PCOS with HFD group (0.1929±0.012, 0.3346±0.103 and 0.3468±0.031) were obviously higher than those in control group (0.2492±0.013, 0.3271±0.093 and 0.3393±0.061), but no significant difference was observed between PCOS group and PCOS with HFD group. It was suggested that MIF may participate in the pathogenesis of PCOS through the MAPK signalling pathway in PCOS rats induced by DHEA.
研究领域:
内分泌学
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生殖生物学
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药理学
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DOI
PubMed
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2023
·
IF 5.6
Wenbo Ge,Zhun Li,Yajun Yang,Xiwang Liu,Zhaohan Zhu,Lixia Bai,Zhe Qin,Xiao Xu,Jianyong Li,Shihong Li
Pathogenic Escherichia coli ( E. coli ) can cause intestinal diseases in humans and livestock, damage the intestinal barrier, increase systemic inflammation, and seriously threaten human health and the development of animal husbandry. In this study, we designed and synthesized a novel conjugate florfenicol sulfathiazole (FST) based on drug combination principles, and investigated its antibacterial activity in vitro and its protective effect on inflammatory response and intestinal barrier function in E. coli O78-infected mice in vivo . The results showed that FST had superior antibacterial properties and minimal cytotoxicity compared with its prodrugs as florfenicol and sulfathiazole. FST protected mice from lethal E. coli infection, reduced clinical signs of inflammation, reduced weight loss, alleviated intestinal structural damage. FST decreased the expression of inflammatory cytokines IL-1β, IL-6, TNF-α, and increased the expression of claudin-1, Occludin, and ZO-1 in the jejunum, improved the intestinal barrier function, and promoted the absorption of nutrients. FST also inhibited the expression of TLR4, MyD88, p-p65, and p-p38 in the jejunum. The study may lay the foundation for the development of FST as new drugs for intestinal inflammation and injury in enteric pathogen infection.
研究领域:
药理学
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微生物学
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免疫学
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兽医学
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DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2023
·
IF 15.1
Jiale Chen,Zhixiang Mu,Dongfan Chen,Chen Huang,Ting Jin,Lin Li,Youyun Zeng,Qiang Zhou,Yanmei Zhang,Hongli Mao,Hui Deng,Xinkun Shen,Hong Yang,Xiaojun Cai
Smart hydrogel dressings capable of simultaneously highly effective antimicrobial, anti-inflammatory, and promoting re-epithelialization and angiogenesis are urgently needed for the management of diabetic wounds. Herein, a H 2 S-releasing multifunctional hydrogel was developed by utilizing the dynamic Schiff base reaction between carboxymethyl chitosan (CMC) and polyhexamethylene guanidine (PHMG)-modified aldehyde F108 (PFC). Diallyl trisulfide (DATS) was encapsulated into the PFC nanoparticles. Apart from possessing the essential properties necessary for an idealized hydrogel dressing, such as excellent injectability, tissue adhesion, self-healing, and stimulus–response degradation, the [email protected] &CMC also utilized the synergistic effect of the PHMG and DATS to provide an efficient antimicrobial effect; the H 2 S was slowly released from the DATS under the action of GSH and exerted excellent anti-inflammatory effects, by inhibiting the expression of p-ERK and p-STAT3 in activated macrophages, and promoting macrophage polarization to the M2 phenotype. Strikingly, following the completion of the efficient antimicrobial and anti-inflammatory effects, the continuously generated H 2 S further significantly accelerated the proliferation, migration, and vascularization of endothelial cells by extending the activation of the p-p38 and p-ERK1/2. Owing to superior performances, [email protected] &CMC significantly promoted the healing of diabetic wounds induced by streptozotocin with good biocompatibility. This study demonstrates that [email protected] &CMC is a versatile hydrogel dressing with great potential for the management of diabetic wounds.
研究领域:
生物医学工程
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材料科学
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药剂学
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伤口愈合
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糖尿病管理
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产品关联
DOI
高影响因子
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
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2021
·Vol. 25
·期 15
·7472-7484
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IF 5.31
Pengfei Zhu,Zhengchao Wang,Zhenxing Sun,Bokai Liao,Yu Cai
Osteoarthritis (OA) is a common joint disease that mainly affects the diarthrodial joints. Treatments for OA include non-pharmacological interventions, topical and oral therapies, intra-articular therapies and joint surgery. However, all the treatments mentioned above mainly aim to control the symptoms instead of improving or reversing the joint condition. In this research, we observed the effect of recombinant platelet-derived growth factor (PDGF)-BB on OA in a monosodium iodoacetate (MIA)–induced rat model and revealed the possible mechanisms. In vitro, the level of inflammation in the chondrocytes was gradually alleviated, and the apoptosis rate was gradually decreased by PDGF-BB at increasing concentrations. The levels of p-p38, Bax and caspase-3 decreased, and the level of p-Erk increased with increasing PDGF-BB concentration. In vivo, PDGF-BB could significantly reverse chondrocyte and matrix loss. Furthermore, high concentrations of PDGF-BB could alleviate cartilage hyperplasia to remodel the tissue. The level of collagen II was up-regulated, and the levels of collagen X and apoptosis were down-regulated by increasing concentrations of PDGF-BB. In conclusion, recombinant PDGF-BB alleviated OA by down-regulating caspase-3-dependent apoptosis. The effects of PDGF-BB on OA mainly include inhibiting chondrocyte loss, reducing cartilage hyperplasia and osteophyte formation, and regulating collagen anabolism.
研究领域:
骨科
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分子生物学
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细胞生物学
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药理学
✓ 已验证
DOI
PubMed
高影响因子
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