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Dual-directional regulation of spinal cord injury and the gut microbiota

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Neural Regeneration Research 2024年第3期19卷 548-556页

作者： Yinjie Cui Jingyi Liu Xiao Lei Shuwen Liu Haixia Chen Zhijian Wei Hongru Li Yuan Yang Chenguang Zheng Zhongzheng Li Academy of Medical Engineering and Translational Medicine Tianjin UniversityTianjinChina School of Medical Technology Tianjin University of Traditional Chinese MedicineTianjinChina Research Center of Experimental Acupuncture Science Tianjin University of Traditional Chinese MedicineTianjinChina International Cooperation and Exchange Office Chengdu University of Traditional Chinese MedicineChengduSichuan ProvinceChina International Cooperation Base of Spinal Cord Injury Tianjin Key Laboratory of Spine and Spinal Cord InjuryDepartment of OrthopedicsTianjin Medical University General HospitalTianjinChina Department of Orthopedics Qilu Hospital of Shandong UniversityJinanShandong ProvinceChina

There is increasing evidence that the gut microbiota affects the incidence and progression of central nervous system diseases via the brain-gut axis.The spinal cord is a vital important part of the central nervous system;however,the underlying association between spinal cord injury and gut interactions remains unknown.Recent studies suggest that patients with spinal cord injury frequently experience intestinal dysfunction and gut dysbiosis.Alterations in the gut microbiota can cause disruption in the intestinal barrier and trigger neurogenic inflammatory responses which may impede recovery after spinal cord injury.This review summarizes existing clinical and basic research on the relationship between the gut microbiota and spinal cord injury.Our research identified three key points.First,the gut microbiota in patients with spinal cord injury presents a key characteristic and gut dysbiosis may profoundly influence multiple organs and systems in patients with spinal cord injury.Second,following spinal cord injury,weakened intestinal peristalsis,prolonged intestinal transport time,and immune dysfunction of the intestine caused by abnormal autonomic nerve function,as well as frequent antibiotic treatment,may induce gut dysbiosis.Third,the gut microbiota and associated metabolites may act on central neurons and affect recovery after spinal cord injury;cytokines and the Toll-like receptor ligand pathways have been identified as crucial mechanisms in the communication between the gut microbiota and central nervous system.Fecal microbiota transplantation,probiotics,dietary interventions,and other therapies have been shown to serve a neuroprotective role in spinal cord injury by modulating the gut microbiota.Therapies targeting the gut microbiota or associated metabolites are a promising approach to promote functional recovery and improve the complications of spinal cord injury.

关键词： chemokines cytokines gut microbiota NLRP3 spinal cord injury Toll-like receptor ligand tryptophan

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The secondary injury cascade after spinal cord injury: an analysis of local cytokine/chemokine regulation

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Neural Regeneration Research 2024年第6期19卷 1308-1317页

作者： Daniel J.Hellenbrand Charles M.Quinn Zachariah J.Piper Ryan T.Elder Raveena R.Mishra Taylor L.Marti Phoebe M.Omuro Rylie M.Roddick Jae Sung Lee William L.Murphy Amgad S.Hanna Department of Neurosurgery University of Wisconsin-Madison School of Medicine and Public Health Department of Biomedical Engineering University of Wisconsin-Madison Department of Orthopedics and Rehabilitation University of Wisconsin-Madison Department of Materials Science and Engineering University of Wisconsin-Madison Forward BIO Institute University of Wisconsin-Madison

After spinal cord injury, there is an extensive infiltration of immune cells, which exacerbates the injury and leads to further neural degeneration. Therefore, a major aim of current research involves targeting the immune response as a treatment for spinal cord injury. Although much research has been performed analyzing the complex inflammatory process following spinal cord injury, there remain major discrepancies within previous literature regarding the timeline of local cytokine regulation. The objectives of this study were to establish an overview of the timeline of cytokine regulation for 2 weeks after spinal cord injury, identify sexual dimorphisms in terms of cytokine levels, and determine local cytokines that significantly change based on the severity of spinal cord injury. Rats were inflicted with either a mild contusion, moderate contusion, severe contusion, or complete transection, 7 mm of spinal cord centered on the injury was harvested at varying times post-injury, and tissue homogenates were analyzed with a Cytokine/Chemokine 27-Plex assay. Results demonstrated pro-inflammatory cytokines including tumor necrosis factor α, interleukin-1β, and interleukin-6 were all upregulated after spinal cord injury, but returned to uninjured levels within approximately 24 hours post-injury, while chemokines including monocyte chemoattractant protein-1 remained upregulated for days post-injury. In contrast, several anti-inflammatory cytokines and growth factors including interleukin-10 and vascular endothelial growth factor were downregulated by 7 days post-injury. After spinal cord injury, tissue inhibitor of metalloproteinase-1, which specifically affects astrocytes involved in glial scar development, increased more than all other cytokines tested, reaching 26.9-fold higher than uninjured rats. After a mild injury, 11 cytokines demonstrated sexual dimorphisms; however, after a severe contusion only leptin levels were different between female and male rats. In conclusion, pro-inflammatory cytokines initiate the inf

关键词： astrocytes chemokines cytokines inflammation macrophages microglia secondary damage spinal cord injury

Immunoglobulin G-mediated food intolerance and metabolic syndrome influence the occurrence of reflux esophagitis in Helicobacter pylori-infected patients

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World Journal of Gastroenterology 2024年第8期30卷 855-862页

作者： Li-Hui Wang Bin-Bin Su Sheng-Shu Wang Guan-Chao Sun Kun-Ming Lv Yi Li Hui Shi Qian-Qian Chen College Chinese PLA General HospitalBeijing 100853China Department of Gastroenterology Second Medical Center of Chinese PLA General HospitalBeijing 100853China Institute of Geriatrics The 2nd Medical CenterBeijing Key Laboratory of Aging and GeriatricsNational Clinical Research Center for Geriatrics DiseasesSecond Medical Center of Chinese PLA General HospitalBeijing 100853China Department of Gastroenterology First Medical Center of Chinese PLA General HospitalBeijing 100853China

BACKGROUND Reflux esophagitis has an increasing prevalence and complex and diverse symptoms.Identifying its risk factors is crucial to understanding the etiology,prevention,and management of the disease.The occurrence of reflux esophagitis may be associated with food reactions,Helicobacter pylori(H.pylori)infection,and metabolic syndromes.AIM To investigate the risk factors for reflux esophagitis and analyze the effects of immunoglobulin(Ig)G-mediated food intolerance,H.pylori infection,and metabolic syndrome on reflux esophagitis.METHODS Outpatients attending the Second Medical Center of the PLA General Hospital between 2017 and 2021 were retrospectively enrolled.The patients’basic information,test results,gastroscopy results,H.pylori test results,and IgG-mediated food intolerance results were collected.Multivariate logistic regression analysis was used to analyze risk factors for reflux esophagitis.Statistical mediation analysis was used to evaluate the effects of IgG-mediated food intolerance and metabolic syndrome on H.pylori infection affecting reflux esophagitis.RESULTS A total of 7954 outpatients were included;the prevalence of reflux esophagitis,IgG-mediated food intolerance,H.pylori infection,and metabolic syndrome were 20.84%,61.77%,35.91%,and 60.15%,respectively.Multivariate analysis showed that the independent risk factors for reflux esophagitis included IgG-mediated food intolerance(OR=1.688,95%CI:1.497-1.903,P<0.00001)and metabolic syndrome(OR=1.165,95%CI:1.030-1.317,P=0.01484),and the independent protective factor for reflux esophagitis was H.pylori infection(OR=0.400,95%CI:0.351-0.456,P<0.00001).IgG-mediated food intolerance had a partially positive mediating effect on H.pylori infection as it was associated with reduced occurrence of reflux esophagitis(P=0.0200).Metabolic syndrome had a partially negative mediating effect on H.pylori infection and reduced the occurrence of reflux esophagitis(P=0.0220).CONCLUSION Patients with IgG-mediated food intolerance and metabolic syndrome were at higher ris

关键词： Gastroesophageal reflux Esophagitis Food intolerance Metabolic syndrome Helicobacter pylori chemokines

chemokines in homeostasis and diseases

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Cellular & Molecular Immunology 2018年第4期15卷 324-334页

作者： Keqiang Chen Zhiyao Bao Peng Tang Wanghua Gong Teizo Yoshimura Ji Ming Wang Cancer and Inflammation Program Center for Cancer ResearchNational Cancer Institute at FrederickFrederickMD 21702USA Department of Pulmonary&Critical Care Medicine Ruijin HospitalShanghai Jiaotong University School of MedicineShanghai 200025P.R.China Department of Breast Surgery Southwest HospitalThird Military Medical UniversityChongqing 400038China Basic Research Program Leidos Biomedical ResearchInc.FrederickMD 21702USA Department of Pathology and Experimental Medicine Graduate School of MedicineDentistry and Pharmaceutical SciencesOkayama UniversityOkayama 700-8558Japan

For the past twenty years,chemokines have emerged as a family of critical mediators of cell migration during immune surveillance,development,inflammation and cancer progression.chemokines bind to seven transmembrane G protein-coupled receptors(GPCRs)that are expressed by a wide variety of cell types and cause conformational changes in trimeric G proteins that trigger the intracellular signaling pathways necessary for cell movement and activation.Although chemokines have evolved to benefit the host,inappropriate regulation or utilization of these small proteins may contribute to or even cause diseases.Therefore,understanding the role of chemokines and their GPCRs in the complex physiological and diseased microenvironment is important for the identification of novel therapeutic targets.This review introduces the functional array and signals of multiple chemokine GPCRs in guiding leukocyte trafficking as well as their roles in homeostasis,inflammation,immune responses and cancer.

关键词： chemokines chemotaxis diseases GPCRs homeostasis inflammatory cells

chemokines and hepatocellular carcinoma

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World Journal of Gastroenterology 2010年第15期16卷 1832-1836页

作者： Huang, Fan Geng, Xiao-Ping Anhui Med Univ Affiliated Hosp 1 Dept Hepatobiliary Surg Hefei 230022 Anhui Peoples R China

chemokines play a paramount role in tumor progres-sion. In hepatocellular carcinoma (HCC) progression, chemokines and their receptors play an intricate role. Currently, chemokines and their receptors such as the CXCL12-CXCR4 axis, CX3CL1-CX3CR1 axis and the CCL20-CCR6 axis have received much research attention. Although a large number of studies show that these axes are strongly associated with HCC, the exact mechanism by which these axes promote the growth and progression of HCC remains unknown. In this paper, several chemokines and their receptor interactions in HCC progression, growth and metastasis and immune response to HCC are reviewed.

关键词： chemokines Hepatocellular carcinoma

Expression of Pref-1 and Related chemokines during the Development of Rat Mesenteric Lymph Nodes

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Biomedical and Environmental Sciences 2018年第7期31卷 507-514页

作者： PENG Yan JIA Li Min LI Bao Xin XIE Li Ping XIE Zun Jiang ZHENG Jin Hua Department of Anatomy Basic Medical Science College Harbin Medical University Department of Pharmacology Pharmacy College Harbin Medical University

Objective The aim of this study was to investigate the ability of Pref-1~＋ adipocyte progenitor cells to mobilize into mesenteric lymph nodes（MLNs） and the dynamic expression of related chemokines during the development of rat MLNs. Methods Immunohistochemical analyses were used to detect the expression of Pref-1 and related chemokines. Transmission electron microscopy（TEM） was used to observe the changes in ultrastructure of MLNs. Results Cells containing lipid droplets were found in all rat MLNs at embryonic day（E） 18.5, 2 and 6 weeks（w） after birth, and they were similar to fibroblastic reticular cells（FRCs） or follicular dendritic cells（FDCs） under TEM. Pref-1~＋ adipocyte progenitor cells were found in all MLNs. The expression level of Pref-1 was significantly increased at 2 w after birth and decreased at 6 w after birth. The tendency of Cxcl12 expression was consistent with that of Pref-1 and was positively correlated with the expression of Pref-1（P 〈 0.01; r = 0.897）. At E18.5, Cxcl13, and Ccr7 were significantly expressed in the MLN anlage, but the expression level of Ccl21 was low. The expression level of Cxcl13, Ccr7, and Ccl21 in MLN were significantly increased at 2 w after birth（P 〈 0.05）, while the expression of Ccr7 and Ccl21 were significantly decreased at 6 w after birth（P 〈 0.05）. Conclusion Adipocyte progenitor cells are involved in the rat MLNs development through differentiation into FRC and FDC. The expression of the relevant chemokines during the development of MLNs is dynamic and may be related to the maintenance of lymph nodes self-balance state.

关键词： Mesenteric lymph nodes Development Rat Ultrastructure Adipocyte progenitor cells chemokines

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CXC family of chemokines as prognostic or predictive biomarkers and possible drug targets in colorectal cancer

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World Journal of Gastroenterology 2018年第42期24卷 4738-4749页

作者： Sara Cabrero-de las Heras Eva Martínez-Balibrea Program Against Cancer Therapeutic Resistance Catalan Institute of OncologyGermans Trias i Pujol health research institute Program of Predictive and Personalized Cancer Medicine Germans Trias i Pujol health research institute

Colorectal cancer(CRC) is the third most common cancer in men and the second most common cancer in women,worldwide. In the early stages of the disease, biomarkers predicting early relapse would improve survival rates.In metastatic patients, the use of predictive biomarkers could potentially result in more personalized treatments and better outcomes. The CXC family of chemokines(CXCL1 to 17) are small(8 to 10 kDa) secreted proteins that attract neutrophils and lymphocytes. These chemokines signal through chemokine receptors(CXCR) 1 to 8.Several studies have reported that these chemokines and receptors have a role in either the promotion or inhibition of cancer, depending on their capacity to suppress or stimulate the action of the immune system, respectively.In general terms, activation of the CXCR1/CXCR2 pathway or the CXCR4/CXCR7 pathway is associated with tumor aggressiveness and poor prognosis; therefore,the specific inhibition of these receptors is a possible therapeutic strategy. On the other hand, the lesser known CXCR3 and CXCR5 axes are generally considered to be tumor suppressor signaling pathways, and their stimulation has been suggested as a way to fight cancer.These pathways have been studied in tumor tissues(using immunohistochemistry or measuring mRNA levels)or serum [using enzyme-linked immuno sorbent assay(ELISA) or multiplexing techniques], among other sample types. Common variants in genes encoding for the CXC chemokines have also been investigated as possible biomarkers of the disease. This review summarizes themost recent findings on the role of CXC chemokines and their receptors in CRC and discusses their possible value as prognostic or predictive biomarkers as well as the possibility of targeting them as a therapeutic strategy.

关键词： Biomarkers Treatment Chemotherapy Oxaliplatin Irinotecan Immunotherapy Colorectal cancer CXC chemokines Immune system Bevacizumab

Chemokine Receptors CCR1, CCR3, CCR7 and chemokines CX3CL1 and CCL5 are Significantly Up-Regulated and Very Reliable for Acute Rejection Diagnosis of Kidney Transplants

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Open Journal of Nephrology 2023年第2期13卷 126-149页

作者： Paula Xavier Dias-Pinto José Gerardo G. Oliveira Portuguese Blood and Transplantation Institute Porto Portugal Faculty of Medicine University of Porto Porto Portugal CINTESIS FMUP Porto Portugal

Background: The allo-immune response following organ transplantation constitutes one of the main determinants concerning both short- and long- term outcomes in renal graft recipients. chemokines and their receptors play a diversified and important role, either homeostatic or inflammatory and direct different immune-competent cell types to the allograft. While deeply studied in the last two decades, controversy persists as a result of chemokines’ pleiotropic actions. We report our analysis of CCR1, CCR3, CCR7, CCL5 and CX3CL1 expression or synthesis by graft-infiltrating cells in human kidney transplants (KTx). At the same time, we tested their robustness in diagnosing acute rejection. Methods: Fine-needle aspiration biopsies (Fnab) were performed either on days 7 or 14 post-transplantation among stable KTx and on the day of acute rejection (AR) diagnosis. Fnab cytopreparations were studied by the enzymatic avidin-biotin complex staining for CCR1, CCR3, CCR7 and CX3CL1. From another subgroup of cases, Fnab samples were cultured for 48 hours and the supernatants were analysed for CCL5 by ELISA. Results: The group of AR cases showed a significantly up-regulated expression of CCR1, CCR3, CCR7 and CX3CL1 and a significantly higher synthesis of CCL5. The positive predictive values were respectively 92%, 97%, 85%, 76% and 78% and negative predictive values were by the same order, 100%, 73%, 100%, 98% and 83%. Conclusions: Our study permits us to advance that CCR1 and CCR3 play a significant and non-redundant role in acute rejection, and it is the first report of CCR3 association with rejection, probably related to CCL5. The presence inside the graft of significant up-regulation for CCR7 surmises that part of antigen presentation may be performed there without being restricted to secondary lymphoid sites. Our results with CX3CL1 confirm other reports.

关键词： Kidney Transplants Aspiration Biopsies Acute Rejection chemokines Chemokine Receptors

Analysis on the types of chemokines expressed by the murine thymic epithelial cell line MTEC1

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Chinese Science Bulletin 2000年第12期45卷 1098-1101页

作者： Laiping Xie Xiaoping Qian Sunyou Gong Weifeng Chen Beijing Med Univ Dept Immunol Beijing 100083 Peoples R China

Six kinds of chemokines including SDF-1α, IP-10, KG, RANTES, MCP-1 and Lymphotactin have been amplified using the primers designed by ourselves with RT-PCR from the total RNA of a medullary-type murine thymic epithelial cell line MTEC1 cells. The amplified cDNA fragments of the chemokines have been identified by nucleotide sequencing and Northern blot analysis. The results demonstrate that there are two different splicing forms of SDF-1 mRNA existing in MTEC1. The concentrated culture supernatant of MTEC1 shows an intermediate level of chemotaxis to CD4-CD8- thymocytes, which conforms to the biological function of SDF-1.

关键词： thymic epithelial cells chemokines analysis.

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