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MicroRNA regulation of innate immune responses in epithelial cells

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Cellular & Molecular Immunology 2011年第5期8卷 371-379页

作者： Rui Zhou Steven P O’Hara Xian-Ming Chen Department of Microbiology and Immunology Creighton University School of MedicineOmahaNEUSA Division of Gastroenterology and Hepatology Department of Internal MedicineMayo Clinic College of MedicineRochesterMNUSA

Mucosal surface epithelial cells are equipped with several defense mechanisms that guard against *** studies indicate that microRNAs(miRNAs)mediate post-transcriptional gene suppression and may be a critical component of the complex regulatory networks in epithelial immune *** of miRNA genes in epithelial cells can be elaborately controlled through pathogen recognition receptors,such as Toll-like receptors(TLRs),and associated nuclear factor kappaB(NF-kB)and mitogen-activated protein kinase(MAPK)pathways,and ultimately nuclear transcription factor associated-transactivation and *** of these intracellular signaling pathways may also modulate the process of miRNA ***,miRNAs may modulate epithelial immune responses at every step of the innate immune network,including production and release of cytokines/chemokines,expression of adhesion and costimulatory molecules,shuttling of miRNAs through release of exosomes and feedback regulation of immune ***,miRNAs act as critical regulators to the fine-tuning of epithelial immune responses.

关键词： epithelial cells immune responses miRNAs posttranscriptional regulation TLRs

Potential role of chitinase 3-like-1 in inflammation-associated carcinogenic changes of epithelial cells

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World Journal of Gastroenterology 2009年第42期15卷 5249-5259页

作者： Katrin Eurich Mayuko Segawa Satoko Toei-Shimizu Emiko Mizoguchi Gastrointestinal Unit Department of MedicineMassachusetts General HospitalHarvard Medical SchoolBostonMA 02114United States Center for the Study of Inflammatory Bowel Disease Massachusetts General HospitalHarvard Medical SchoolBostonMA 02114United States

The family of mammalian chitinases includes members both with and without glycohydrolase enzymatic activity against chitin, a polymer of N-acetylglucosamine. Chitin is the structural component of fungi, crustaceans, insects and parasitic nematodes, but is completely absent in mammals. Exposure to antigens containing chitin- or chitin-like structures sometimes induces strong T helper type-I responses in mammals, which may be associated with the induction of mammalian chitinases. Chitinase 3-like-1 （CHI3L1）, a member of the mammalian chitinase family, is induced specifically during the course of inflammation in such disorders as inflammatory bowel disease, hepatitis and asthma. In addition, CHI3L1 is expressed and secreted by several types of solid tumors including glioblastoma, colon cancer, breast cancer and malignant melanoma. Although the exact function of CHI3L1 in inflammation and cancer is still largely unknown, CHI3L1 plays a pivotal role in exacerbating the inflammatory processes and in promoting angiogenesis and remodeling of the extracellular matrix. CHI3L1 may be highly involved in the chronic engagement of inflammation which potentiates development of epithelial tumorigenesis presumably by activating the mitogen-activated protein kinase and the protein kinase B signaling pathways. Anti-CHI3L1 antibodies or pan-chitinase inhibitors may have the potential to suppress CHI3Ll-mediated chronic inflammation and the subsequent carcinogenic change in epithelial cells.

关键词： Mammals Chitinase 3-1ike 1 Colon epithelial cells Inflammation Colitis Colon neoplasms Inflammatory bowel disease

Different cytokine response of primary colonic epithelial cells to commensal bacteria

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World Journal of Gastroenterology 2005年第22期11卷 3375-3384页

作者： Jing-GangLan SheenaMargaretCruickshank JoyCarmelinaIndiraSingh MarkFarrar JamesPeterAlanLodge PeterJohnFelsburg SimonRichardCarding SchoolofBiochemistryandMicrobiology TheUniversityofLeedsLeedsLS29JTUnitedKingdom GeneralSurgery MedicineandAnaesthesiaSchoolofMedicineTheUniversityofLeedsLeedsLS29JTUnitedKingdom

AIM: To determine if primary murine colonic epithelial cells (CEC) respond to commensal bacteria and discriminate between different types of bacteria. METHODS: A novel CEC: bacteria co-culture system was used to compare the ability of the colonic commensal bacteria, Bacteroides ovatus, E coli(SLF) and Lactobacillus rhamnosus (LGG) to modulate production of different cytokines (n = 15) by primary CEC. Antibody staining and flow cytometry were used to investigate Toll-like receptor (TLR) expression by CEC directly ex vivo and TLR responsiveness was determined by examining the ability of TLR ligands to influence CEC cytokine production. RESULTS: Primary CEC constitutively expressed functional TLR2 and TLR4. Cultured in complete medium alone, CEC secreted IL-6, MCP-1 and IP-10 the levels of which were significantly increased upon addition of the TLR ligands peptidoglycan (PGN) and lipopolysaccharide (LPS). Exposure to the commensal bacteria induced or up-regulated different patterns of cytokine production and secretion.E coli induced production of MIP-1α/β and p defensin3 whereas B. ovatus and L. rhamnosus exclusively induced MCP-1 and MIP-2α expression, respectively. TNFa, RANTES and MEC were induced or up-regulated in response to some but not all of the bacteria whereas ENA78 and IP-10 were up-regulated in response to all bacteria. Evidence of bacterial interference and suppression of cytokine production was obtained from mixed bacterial: CEC co-cultures. Probiotic LGG suppressed E coli- and B. ovatus-induced cytokine mRNA accumulation and protein secretion. CONCLUSION: These observations demonstrate the ability of primary CEC to respond to and discriminate between different strains of commensal bacteria and identify a mechanism by which probiotic bacteria (LGG) may exert anti-inflammatory effects in vivo.

关键词： epithelial cells Colon Commensal bacteria Cytokines Chemokines

Epithelium-specific ets transcription factor 2 upregulates cytokeratin 18 expression in pulmonary epithelial cells through an interaction with cytokeratin 18 intron 1

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Cell Research 2005年第6期15卷 423-429页

作者： Deanna YANIW,Jim HU Programme in Lung Biology Research and the Canadian Institutes of Health Research Group in Lung Development 24] Canada M5S 1A 8] Canada M5S 1A Hospital for Sick Children Toronto Canada M5G 1X8 Institute of Medical Science University of Toronto Toronto Programme in Lung Biology Research and the Canadian Institutes of Health Research Group in Lung Development Hospital for Sick Children Toronto Canada M5G 1X8 Institute of Medical Science University of Toronto Toronto Canada M5S 1A1 Departments of Paediatrics University of Toronto Toronto Canada M5S 1A1 Laboratory Medicine and Pathbiology University of Toronto Toronto

The role of Ese-2, an Ets family transcription factor, in gene regulation is not known. In this study, the interactionbetween Ese-2 and cytokeratin 18 (K18) intron 1 was characterized in lung epithelial cells. Reporter gene assays showedEse-2 was able to upregulate K18 intron 1 enhanced reporter gene expression by approximately 2-fold. We found thatfull length Ese-2 did not bind DNA strongly, therefore truncated versions of the protein, containing the ETS domain orPointed domain, were created and tested in electrophoresis mobility shift assays. Multiple interactions between the ETSdomain and putative DNA binding sites within K18 intron 1 were observed, which led to the determination of a possibleEse-2 DNA binding consensus sequence. These experiments suggest that Ese-2 could play a role in the regulation ofK18 expression in lung epithelial cells.

关键词： transcription factor epithelial cells cytokeratin 18 airway gene regulation.

Three Tiaobu Feishen formulae reduces cigarette smoke-induced inflammation in human airway epithelial cells

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Journal of Traditional Chinese Medicine 2020年第3期40卷 386-392页

作者： Dong Haoran Liu Xuefang Zheng Wanchun Feng Suxiang Li Jiansheng Qin Yanqin Wu Yaosong Chen Yulong Yin Sugai Zhao Peng Henan Key Laboratory of Chinese Medicine for Respiratory Disease Henan University of Chinese MedicineZhengzhou 450046China Collaborative Innovation Center for Respiratory Disease Diagnosis and Treatment&Chinese Medicine Development of Henan Province Henan University of Chinese MedicineZhengzhou 450046China

OBJECTIVE: To investigate the therapeutic efficacy of Tiaobu Feishen formulae(TBFS) on cigarette smoke-induced inflammation in vitro using lipopolysaccharide(LPS)-induced and cigarette smoke extract(CSE)-induced NCI-H292 ***: We evaluated the inhibitory effects of Bufei Jianpi formula(BJF), Bufei Yishen formula(BYF), and Yiqi Zishen formula(YZF) on the expressions of inflammatory cytokines including tumor necrosis factor(TNF)-α and interleukin(IL)-8, matrix metalloproteinase(MMP)-9, tissue inhibitor of matrix metalloprotease(TIMP)-1, and superoxide dismutase(SOD) in H292 cells stimulated with LPS or CSE. Their related transcription factors and signaling pathways were also ***: BJF, BYF, and YZF significantly inhibited the LPS-or CSE-induced expressions of TNF-α, IL-8,MMP-9, TIMP-1, and SOD in H292 cells, and suppressed the activation of transcription factors including nuclear transcription factor(NF)-κB, activator protein(AP)-1, and signal transducers and activators of transcription(STAT) 3 and their corresponding pathways, including NF-κB, mitogen-activated protein kinase(MAPK), STAT3, and peroxisome proliferator-activated receptor(PPAR).CONCLUSION: BJF, BYF, and YZF effectively suppressed inflammatory responses, protease-antiprotease imbalance, and oxidative stress induced by LPS and CSE, an effect that was closely associated with the inhibition of the NF-κB, MAPK, STAT3, and PPAR pathways.

关键词： Pulmonary disease chronic obstructive Lipopolysaccharides Cigarette smoking Inflammation epithelial cells Tiaobu Feishen formulae

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Diethyldithiocarbamate inhibits iNOS expression in human lens epithelial cells stimulated by IFN-gamma and LPS

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Acta Pharmacologica Sinica 2005年第3期26卷 359-363页

作者： Yoshimasa ITO Japan Osaka 577-8502 School of Pharmacy Pharmaceutical Research und Technology Institute Kinki University

Aim:To investigate the biological activity of human lens epithelial cells (HLEC)in producing inducible nitric oxide synthase (iNOS) and nitric oxide (NO),and toassesse the effect of diethyldithiocarbamate (DDC) on iNOS mRNA levels andexpression of ***:The human lens epithelial cell line SRA 01/04 wasused in this ***-quantitative reverse transcription polymerase chainreaction (RT-PCR) and Western blotting were used to detect,respectively,iNOSmRNA expression and protein ***:A costimulation by inter-feron gamma (IFN-γ) and lipopolysaccharide (LPS) was necessary for iNOS ex-pression in *** expression of iNOS was significantly reduced in a dose-dependent manner by adding DDC from 10 μmol/L to 1 mmol/***:The expression of iNOS in HLEC needs co-stimulation with IFN-γ and LPS and itis inhibited by DDC.

关键词： human lens epithelial cells inducible nitric oxide synthase interferon gamma lipopolysaccharide diethyldithiocarbamate

Detection of *** DNA in gastric epithelial cells by in situ hybridization

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World Journal of Gastroenterology 2002年第2期8卷 305-307页

作者： Xin-Liang Lu Ke-Da Oian Xun-Qiu Tang Yong-Liang Zhu Qin Du,Department of Digestive Diseases,Second Affiliated Hospital,Zhejiang University Medical College,Hangzhou 310009,Zhejiang Province,China Department of Digestive Diseases Second Affiliated Hospital Zhejiang University Medical College Hangzhou 310009 Zhejiang Province China. luxl@***

AIM: To investigate the presence of *** DNA within gastric epithelial cells in patients with *** infection and its possible carcinogenic mechanism. METHODS: Total 112 patients, with pathologically confirmed chronic superficial gastritis, chronic atrophic gastritis, intestinal metaplasia, atypical hyperplasia or gastric cancer were studied. Among them, 28 were *** negative and 84 *** positive. *** DNA in gastric epithelial cells was detected by GenPoint catalyzed signal amplification system for in situ hybridization. RESULTS: In the *** positive group, zero out of 24 chronic superficial gastritis (0.0%), four out of 25 precancerous changes (16.0%) and thirteen out of 35 gastric cancers (37.1%) showed *** DNA in the nucleus of gastric epithelial cells, the positive rates of *** DNA in the nucleus of gastric epithelial cells were progressively increased in chronic superficial gastritis, precancerous changes and gastric cancer groups (chi(2)=12.56, P=0.002); One out of 24 chronic superficial gastritis (4.2%), eleven out of 25 precancerous changes (44.0%) and thirteen out of 35 gastric cancers (37.1%) showed *** DNA in the cytoplasm of gastric epithelial cells (chi(2)=10.86, P=0.004). In the *** negative group, only one patient with gastric cancer was found *** DNA in the nucleus of gastric epithelial cells; Only two patients, one patient with precancerous changes and another with gastric cancer, showed *** DNA in the cytoplasm of gastric epithelial cells. Furthermore, *** DNA must have been in the cytoplasm as long as it existed in the nucleus of gastric epithelial cells. CONCLUSION: *** DNA exists both in the nucleus and the cytoplasm of gastric epithelial cells in patients with *** infections. The pathological progression from chronic superficial gastritis, precancerous changes to gastric cancer is associated with higher positive rates of *** DNA presence in the nucleus of gastric epitheli

关键词： In Situ Hybridization DNA, Bacterial epithelial cells Gastric Mucosa Helicobacter Infections Helicobacter pylori purification Humans Stomach Diseases

Experimental Study of Plasmid TGF-β1 DNA Gene Transfer with Lipofectamine into Rabbit Corneal epithelial cells In Vitro

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2002年第1期22卷 62-65页

作者：黄琼胡燕华姜发纲陈宏 Department of Ophthalmology Xiehe Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan

To investigate whether the TGF β1 plasmid DNA carried by lipofectamine could be introduced into cultured rabbit corneal epithelial cells, specific expression of the plasmid pMAM TGF β1 in the cultured corneal epithelial cells was studied. Two days after 12 h of transfection of pMAMTGF β1 mediated by lipofectamine into the cultured corneal epithelial cells, the TGF β1 protein expression specific for pMAMTGF β1 in the cells was detected by means of immunohistochemical staining and the positive rate was 23.37 %. The results suggested that foreign plasmid DNA could be effectively delivered into cultured rabbit corneal epithelial cells by means of lipofectamine, and this will provide a promising method of studying TGF β1 on the mechanism of physiology and pathology concerned with corneal epithelial cells.

关键词： cornea epithelial cells gene transfer transforming growth factor beta

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Effect of Pyruvate on Polyol Pathway and Lens epithelial cells Apoptosis in Diabetic Rats

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眼科学报 2006年第4期22卷 259-264页

作者： Yanxiu Qi Jisong Zhang Department of Ophthalmology The First Affiliated Hospital China Medical UniversityShenyang 110001 China

Purpose: To investigate the effect of polyol pathway on lens epithelial cells apoptosis and the activity of caspase-3 and its reversal by pyruvate in diabetic rats. Methods: 220 Wister rats were divided into 3 groups: control group, model group and treatment group. After streptozotocin (STZ) induced cataract, the treatment group received 2% pyruvate in the diet and drinking. The opacification of lens was detected by microscope every 2 weeks. On 4W, 8W and 12W of the experiment, glucose and sorbitol in the lens were quantified by high-performance liquid chromatography. The percentage of lens epithelial cells undergoing apoptosis was measured by Annexin Ⅴ/PI staining. The activity of caspase-3 was analyzed by Western-blot. Results: Studies show that there was significant increase of glucose, sorbitol in lens of model group, the apoptosis rate and caspase-3 activity of lens epithelial cells were also gradually increase. Pyruvate treatment decreased the levels of sotbitol, glucose, lens epithelial cells apoptosis and caspase-3 activity. The progress of cataract was also significantly delayed. Conclusions: Polyol pathway, possibly through regulation of the activity of caspase-3, can induce apoptosis of lens epithelial cell. Pyruvate ingested orally can effective inhibit diabetic cataractogenesis in rats through inhibit polyol pathway.

关键词： Diabetes mellitus Lens epithelial cells Polyol pathway Apoptosis Caspase-3 Pyruvate

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