The effects of CCR7 and related signaling pathways on Leishmania major ‐infected human dendritic cells

Objectives In our research, we aimed to investigate the roles of CC‐chemokine receptor 7 (CCR7) and relevant signaling pathways in Leishmania major‐infected human dendritic cells (DCs). Methods Differentially expressed genes (DEGs) in L. major‐infected human DCs were selected out and visualized usin...

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Veröffentlicht in:Journal of cellular physiology 2019-08, Vol.234 (8), p.13145-13156
Hauptverfasser: Zhao, Yumin, Dang, Zhisheng, Wei, Riming, Gui, Weifeng, Zhang, Yishu, Chong, Shigui
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container_issue 8
container_start_page 13145
container_title Journal of cellular physiology
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creator Zhao, Yumin
Dang, Zhisheng
Wei, Riming
Gui, Weifeng
Zhang, Yishu
Chong, Shigui
description Objectives In our research, we aimed to investigate the roles of CC‐chemokine receptor 7 (CCR7) and relevant signaling pathways in Leishmania major‐infected human dendritic cells (DCs). Methods Differentially expressed genes (DEGs) in L. major‐infected human DCs were selected out and visualized using R program. Kyoto Encyclopedia of Genes and Genomes pathway analysis was conducted for investigation of significantly enriched signaling pathways and Gene Ontology enrichment analysis was carried out for the unveiling of enriched Molecular Functions and Biological Processes in L. major‐infected human DCs. Besides, Hub gene was screened out using weighted gene coexpression network analysis and Cytoscape. In addition, enzyme‐linked immunosorbent assay and real‐time quantitative polymerase chain reaction were used for detection of relative expression of CCR7, interleukin‐12 (IL‐12), and interferon‐γ (IFN‐γ) in L. major‐infected human DCs and western blot analysis was used for detection of relative expression of CCR7 and other proteins in JAK‐STAT signaling pathway in L. major‐infected human DCs. Results CCR7 was upregulated and both chemokine and JAK‐STAT signaling pathway were activated in L. major‐infected human DCs. During the L. major infection, total number of L. major‐infected human DCs were increased, as well as the relative expression levels of CCR7, IL‐12, and IFN‐γ and proteins in the JAK‐STAT signaling pathway. Overexpression of CCR7 not only increased expression levels of IL‐12 and IFN‐γ but also activated the JAK‐STAT signaling pathway to affect the leishmaniasis progression. Conclusion L. major infection‐induced activation of CCR7, as well as JAK2 and STAT1, might well upregulate the expression of BAX yet suppress the expression of both Bcl2 and c‐Jun to affect leishmaniasis progression. 1. Our study showed that CCR7 was up‐regulated and both chemokine and JAK‐STAT signaling pathways were activated in Leishmaniasis. 2. Down‐regulation of CCR7 and inactivation of JAK‐STAT signaling pathway may suppress Leishmaniasis progression in the future.
doi_str_mv 10.1002/jcp.27985
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Methods Differentially expressed genes (DEGs) in L. major‐infected human DCs were selected out and visualized using R program. Kyoto Encyclopedia of Genes and Genomes pathway analysis was conducted for investigation of significantly enriched signaling pathways and Gene Ontology enrichment analysis was carried out for the unveiling of enriched Molecular Functions and Biological Processes in L. major‐infected human DCs. Besides, Hub gene was screened out using weighted gene coexpression network analysis and Cytoscape. In addition, enzyme‐linked immunosorbent assay and real‐time quantitative polymerase chain reaction were used for detection of relative expression of CCR7, interleukin‐12 (IL‐12), and interferon‐γ (IFN‐γ) in L. major‐infected human DCs and western blot analysis was used for detection of relative expression of CCR7 and other proteins in JAK‐STAT signaling pathway in L. major‐infected human DCs. Results CCR7 was upregulated and both chemokine and JAK‐STAT signaling pathway were activated in L. major‐infected human DCs. During the L. major infection, total number of L. major‐infected human DCs were increased, as well as the relative expression levels of CCR7, IL‐12, and IFN‐γ and proteins in the JAK‐STAT signaling pathway. Overexpression of CCR7 not only increased expression levels of IL‐12 and IFN‐γ but also activated the JAK‐STAT signaling pathway to affect the leishmaniasis progression. Conclusion L. major infection‐induced activation of CCR7, as well as JAK2 and STAT1, might well upregulate the expression of BAX yet suppress the expression of both Bcl2 and c‐Jun to affect leishmaniasis progression. 1. Our study showed that CCR7 was up‐regulated and both chemokine and JAK‐STAT signaling pathways were activated in Leishmaniasis. 2. Down‐regulation of CCR7 and inactivation of JAK‐STAT signaling pathway may suppress Leishmaniasis progression in the future.</description><identifier>ISSN: 0021-9541</identifier><identifier>EISSN: 1097-4652</identifier><identifier>DOI: 10.1002/jcp.27985</identifier><identifier>PMID: 30584667</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>BAX protein ; Biological activity ; CC chemokine receptors ; CCR7 ; CCR7 protein ; Chemokines ; Dendritic cells ; Dendritic Cells - immunology ; Dendritic Cells - metabolism ; Encyclopedias ; Enrichment ; Genes ; Genomes ; human dendritic cells ; Humans ; Interferon ; Interleukins ; JAK‐STAT signaling pathway ; Janus kinase 2 ; Janus Kinases - immunology ; Janus Kinases - metabolism ; Leishmania major ; Leishmaniasis ; Leishmaniasis, Cutaneous - immunology ; Leishmaniasis, Cutaneous - metabolism ; Network analysis ; Parasitic diseases ; Polymerase chain reaction ; Proteins ; Receptors, CCR7 - immunology ; Receptors, CCR7 - metabolism ; Signal transduction ; Signal Transduction - physiology ; Signaling ; STAT Transcription Factors - immunology ; STAT Transcription Factors - metabolism ; Stat1 protein ; Vector-borne diseases</subject><ispartof>Journal of cellular physiology, 2019-08, Vol.234 (8), p.13145-13156</ispartof><rights>2018 Wiley Periodicals, Inc.</rights><rights>2019 Wiley Periodicals, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3535-fa0a8fc97014afa9b2502bb388cb42c251a5ba04056ddde7556ad9f85bc3e7df3</citedby><cites>FETCH-LOGICAL-c3535-fa0a8fc97014afa9b2502bb388cb42c251a5ba04056ddde7556ad9f85bc3e7df3</cites><orcidid>0000-0003-3525-3588</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjcp.27985$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjcp.27985$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27923,27924,45573,45574</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30584667$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhao, Yumin</creatorcontrib><creatorcontrib>Dang, Zhisheng</creatorcontrib><creatorcontrib>Wei, Riming</creatorcontrib><creatorcontrib>Gui, Weifeng</creatorcontrib><creatorcontrib>Zhang, Yishu</creatorcontrib><creatorcontrib>Chong, Shigui</creatorcontrib><title>The effects of CCR7 and related signaling pathways on Leishmania major ‐infected human dendritic cells</title><title>Journal of cellular physiology</title><addtitle>J Cell Physiol</addtitle><description>Objectives In our research, we aimed to investigate the roles of CC‐chemokine receptor 7 (CCR7) and relevant signaling pathways in Leishmania major‐infected human dendritic cells (DCs). Methods Differentially expressed genes (DEGs) in L. major‐infected human DCs were selected out and visualized using R program. Kyoto Encyclopedia of Genes and Genomes pathway analysis was conducted for investigation of significantly enriched signaling pathways and Gene Ontology enrichment analysis was carried out for the unveiling of enriched Molecular Functions and Biological Processes in L. major‐infected human DCs. Besides, Hub gene was screened out using weighted gene coexpression network analysis and Cytoscape. In addition, enzyme‐linked immunosorbent assay and real‐time quantitative polymerase chain reaction were used for detection of relative expression of CCR7, interleukin‐12 (IL‐12), and interferon‐γ (IFN‐γ) in L. major‐infected human DCs and western blot analysis was used for detection of relative expression of CCR7 and other proteins in JAK‐STAT signaling pathway in L. major‐infected human DCs. Results CCR7 was upregulated and both chemokine and JAK‐STAT signaling pathway were activated in L. major‐infected human DCs. During the L. major infection, total number of L. major‐infected human DCs were increased, as well as the relative expression levels of CCR7, IL‐12, and IFN‐γ and proteins in the JAK‐STAT signaling pathway. Overexpression of CCR7 not only increased expression levels of IL‐12 and IFN‐γ but also activated the JAK‐STAT signaling pathway to affect the leishmaniasis progression. Conclusion L. major infection‐induced activation of CCR7, as well as JAK2 and STAT1, might well upregulate the expression of BAX yet suppress the expression of both Bcl2 and c‐Jun to affect leishmaniasis progression. 1. Our study showed that CCR7 was up‐regulated and both chemokine and JAK‐STAT signaling pathways were activated in Leishmaniasis. 2. Down‐regulation of CCR7 and inactivation of JAK‐STAT signaling pathway may suppress Leishmaniasis progression in the future.</description><subject>BAX protein</subject><subject>Biological activity</subject><subject>CC chemokine receptors</subject><subject>CCR7</subject><subject>CCR7 protein</subject><subject>Chemokines</subject><subject>Dendritic cells</subject><subject>Dendritic Cells - immunology</subject><subject>Dendritic Cells - metabolism</subject><subject>Encyclopedias</subject><subject>Enrichment</subject><subject>Genes</subject><subject>Genomes</subject><subject>human dendritic cells</subject><subject>Humans</subject><subject>Interferon</subject><subject>Interleukins</subject><subject>JAK‐STAT signaling pathway</subject><subject>Janus kinase 2</subject><subject>Janus Kinases - immunology</subject><subject>Janus Kinases - metabolism</subject><subject>Leishmania major</subject><subject>Leishmaniasis</subject><subject>Leishmaniasis, Cutaneous - immunology</subject><subject>Leishmaniasis, Cutaneous - metabolism</subject><subject>Network analysis</subject><subject>Parasitic diseases</subject><subject>Polymerase chain reaction</subject><subject>Proteins</subject><subject>Receptors, CCR7 - immunology</subject><subject>Receptors, CCR7 - metabolism</subject><subject>Signal transduction</subject><subject>Signal Transduction - physiology</subject><subject>Signaling</subject><subject>STAT Transcription Factors - immunology</subject><subject>STAT Transcription Factors - metabolism</subject><subject>Stat1 protein</subject><subject>Vector-borne diseases</subject><issn>0021-9541</issn><issn>1097-4652</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kElO5DAUQC1EC4phwQWQJTawCHiInWSJIoZGJXULwTr68UBcylDYiUq14wh9Rk7SLgp60RIrL_77T98PoRNKLikh7GqhlpcsK3Kxg2aUFFmSSsF20SzOaFKIlO6jgxAWhJCi4HwP7XMi8lTKbIaap8ZgY61RY8CDxWX5mGHoNfamhdFoHNxLD63rX_ASxmYF64j1eG5caDroHeAOFoPH729_XL-xxJVmihOsTa-9G53CyrRtOEI_LLTBHH--h-j59uapvE_mv-5-ltfzRHHBRWKBQG5VkRGagoWiZoKwuuZ5ruqUKSYoiBpISoTUWptMCAm6sLmoFTeZtvwQnW-9Sz-8TiaMVefC5gLozTCFilFJuJSSkoie_YcuhsnH30aKUZrGoJJF6mJLKT-E4I2tlt514NcVJdUmfxXzVx_5I3v6aZzqzuh_5FfvCFxtgZVrzfp7U_VQ_t4q_wKXHI-b</recordid><startdate>201908</startdate><enddate>201908</enddate><creator>Zhao, Yumin</creator><creator>Dang, Zhisheng</creator><creator>Wei, Riming</creator><creator>Gui, Weifeng</creator><creator>Zhang, Yishu</creator><creator>Chong, Shigui</creator><general>Wiley Subscription Services, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-3525-3588</orcidid></search><sort><creationdate>201908</creationdate><title>The effects of CCR7 and related signaling pathways on Leishmania major ‐infected human dendritic cells</title><author>Zhao, Yumin ; Dang, Zhisheng ; Wei, Riming ; Gui, Weifeng ; Zhang, Yishu ; Chong, Shigui</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3535-fa0a8fc97014afa9b2502bb388cb42c251a5ba04056ddde7556ad9f85bc3e7df3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>BAX protein</topic><topic>Biological activity</topic><topic>CC chemokine receptors</topic><topic>CCR7</topic><topic>CCR7 protein</topic><topic>Chemokines</topic><topic>Dendritic cells</topic><topic>Dendritic Cells - immunology</topic><topic>Dendritic Cells - metabolism</topic><topic>Encyclopedias</topic><topic>Enrichment</topic><topic>Genes</topic><topic>Genomes</topic><topic>human dendritic cells</topic><topic>Humans</topic><topic>Interferon</topic><topic>Interleukins</topic><topic>JAK‐STAT signaling pathway</topic><topic>Janus kinase 2</topic><topic>Janus Kinases - immunology</topic><topic>Janus Kinases - metabolism</topic><topic>Leishmania major</topic><topic>Leishmaniasis</topic><topic>Leishmaniasis, Cutaneous - immunology</topic><topic>Leishmaniasis, Cutaneous - metabolism</topic><topic>Network analysis</topic><topic>Parasitic diseases</topic><topic>Polymerase chain reaction</topic><topic>Proteins</topic><topic>Receptors, CCR7 - immunology</topic><topic>Receptors, CCR7 - metabolism</topic><topic>Signal transduction</topic><topic>Signal Transduction - physiology</topic><topic>Signaling</topic><topic>STAT Transcription Factors - immunology</topic><topic>STAT Transcription Factors - metabolism</topic><topic>Stat1 protein</topic><topic>Vector-borne diseases</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhao, Yumin</creatorcontrib><creatorcontrib>Dang, Zhisheng</creatorcontrib><creatorcontrib>Wei, Riming</creatorcontrib><creatorcontrib>Gui, Weifeng</creatorcontrib><creatorcontrib>Zhang, Yishu</creatorcontrib><creatorcontrib>Chong, Shigui</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of cellular physiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhao, Yumin</au><au>Dang, Zhisheng</au><au>Wei, Riming</au><au>Gui, Weifeng</au><au>Zhang, Yishu</au><au>Chong, Shigui</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The effects of CCR7 and related signaling pathways on Leishmania major ‐infected human dendritic cells</atitle><jtitle>Journal of cellular physiology</jtitle><addtitle>J Cell Physiol</addtitle><date>2019-08</date><risdate>2019</risdate><volume>234</volume><issue>8</issue><spage>13145</spage><epage>13156</epage><pages>13145-13156</pages><issn>0021-9541</issn><eissn>1097-4652</eissn><abstract>Objectives In our research, we aimed to investigate the roles of CC‐chemokine receptor 7 (CCR7) and relevant signaling pathways in Leishmania major‐infected human dendritic cells (DCs). Methods Differentially expressed genes (DEGs) in L. major‐infected human DCs were selected out and visualized using R program. Kyoto Encyclopedia of Genes and Genomes pathway analysis was conducted for investigation of significantly enriched signaling pathways and Gene Ontology enrichment analysis was carried out for the unveiling of enriched Molecular Functions and Biological Processes in L. major‐infected human DCs. Besides, Hub gene was screened out using weighted gene coexpression network analysis and Cytoscape. In addition, enzyme‐linked immunosorbent assay and real‐time quantitative polymerase chain reaction were used for detection of relative expression of CCR7, interleukin‐12 (IL‐12), and interferon‐γ (IFN‐γ) in L. major‐infected human DCs and western blot analysis was used for detection of relative expression of CCR7 and other proteins in JAK‐STAT signaling pathway in L. major‐infected human DCs. Results CCR7 was upregulated and both chemokine and JAK‐STAT signaling pathway were activated in L. major‐infected human DCs. During the L. major infection, total number of L. major‐infected human DCs were increased, as well as the relative expression levels of CCR7, IL‐12, and IFN‐γ and proteins in the JAK‐STAT signaling pathway. Overexpression of CCR7 not only increased expression levels of IL‐12 and IFN‐γ but also activated the JAK‐STAT signaling pathway to affect the leishmaniasis progression. Conclusion L. major infection‐induced activation of CCR7, as well as JAK2 and STAT1, might well upregulate the expression of BAX yet suppress the expression of both Bcl2 and c‐Jun to affect leishmaniasis progression. 1. Our study showed that CCR7 was up‐regulated and both chemokine and JAK‐STAT signaling pathways were activated in Leishmaniasis. 2. Down‐regulation of CCR7 and inactivation of JAK‐STAT signaling pathway may suppress Leishmaniasis progression in the future.</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>30584667</pmid><doi>10.1002/jcp.27985</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0003-3525-3588</orcidid></addata></record>
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subjects BAX protein
Biological activity
CC chemokine receptors
CCR7
CCR7 protein
Chemokines
Dendritic cells
Dendritic Cells - immunology
Dendritic Cells - metabolism
Encyclopedias
Enrichment
Genes
Genomes
human dendritic cells
Humans
Interferon
Interleukins
JAK‐STAT signaling pathway
Janus kinase 2
Janus Kinases - immunology
Janus Kinases - metabolism
Leishmania major
Leishmaniasis
Leishmaniasis, Cutaneous - immunology
Leishmaniasis, Cutaneous - metabolism
Network analysis
Parasitic diseases
Polymerase chain reaction
Proteins
Receptors, CCR7 - immunology
Receptors, CCR7 - metabolism
Signal transduction
Signal Transduction - physiology
Signaling
STAT Transcription Factors - immunology
STAT Transcription Factors - metabolism
Stat1 protein
Vector-borne diseases
title The effects of CCR7 and related signaling pathways on Leishmania major ‐infected human dendritic cells
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