{"id":7337649,"identifier":"DVN/AG0A1Q","persistentUrl":"https://doi.org/10.7910/DVN/AG0A1Q","protocol":"doi","authority":"10.7910","separator":"/","publisher":"Harvard Dataverse","publicationDate":"2023-08-24","storageIdentifier":"file://10.7910/DVN/AG0A1Q","datasetType":"dataset","datasetVersion":{"id":349429,"datasetId":7337649,"datasetPersistentId":"doi:10.7910/DVN/AG0A1Q","storageIdentifier":"file://10.7910/DVN/AG0A1Q","versionNumber":1,"versionMinorNumber":0,"versionState":"RELEASED","latestVersionPublishingState":"RELEASED","deaccessionLink":"","lastUpdateTime":"2023-08-24T05:59:22Z","releaseTime":"2023-08-24T05:59:22Z","createTime":"2023-08-24T05:58:57Z","publicationDate":"2023-08-24","citationDate":"2023-08-24","license":{"name":"CC0 1.0","uri":"http://creativecommons.org/publicdomain/zero/1.0","iconUri":"https://licensebuttons.net/p/zero/1.0/88x31.png","rightsIdentifier":"CC0-1.0","rightsIdentifierScheme":"SPDX","schemeUri":"https://spdx.org/licenses/","languageCode":"en"},"fileAccessRequest":true,"metadataBlocks":{"citation":{"displayName":"Citation Metadata","name":"citation","fields":[{"typeName":"title","multiple":false,"typeClass":"primitive","value":"Prenatal inflammation exposure accelerates lung cancer tumorigenesis in offspring mouse: possible links to IRE1α/XBP1-mediated M2-like polarization of TAMs and PD-L1 up-expression"},{"typeName":"author","multiple":true,"typeClass":"compound","value":[{"authorName":{"typeName":"authorName","multiple":false,"typeClass":"primitive","value":"Ma Jingbo"}}]},{"typeName":"datasetContact","multiple":true,"typeClass":"compound","value":[{"datasetContactName":{"typeName":"datasetContactName","multiple":false,"typeClass":"primitive","value":"Rand, Fei"},"datasetContactEmail":{"typeName":"datasetContactEmail","multiple":false,"typeClass":"primitive","value":"feiran230824@163.com"}}]},{"typeName":"dsDescription","multiple":true,"typeClass":"compound","value":[{"dsDescriptionValue":{"typeName":"dsDescriptionValue","multiple":false,"typeClass":"primitive","value":"Abstract\nPrenatal inflammation exposure (PIE), as a key event during pregnancy, can strongly increase the disease susceptibility in offspring such as lung cancer and a variety of other cancers. To investigate the mechanism of PIE on lung cancer tumorigenesis, two-stage carcinogenesis model in which prenatal BALB/c mice were exposed to 50 μg/kg LPS were adopted. Then, offspring at 16 weeks of age were intraperitoneally instilled with urethane (1g/kg, weekly) to induce lung cancer for 4 weeks. At the 48 weeks of age, mice were killed and lung tissues from PIE and Control groups were collected for HE staining, immunohistochemistry assay, immunofluorescence assay, and Luminex MAGPIX®-based assay. Additionally, CD11b+F4/80+ tumor-associated macrophages (TAMs) were sorted out from lung tumor tissues by cell sorting technique. Flow cytometry was employed to evaluate the effect of PIE on the extent of M2-like polarization of TAMs and PD-L1 expression. Results displayed that the number of lung surface tumor nodules and lung organ index in PIE group was higher than those of Control group. HE analysis revealed more lung lesion changes, including atypical hyperplasia and intrapulmonary metastases in the offspring from prenatally LPS treated mice. Immunohistochemistry assay showed the positive cells of PCNA, MMP-9 and Vimentin in the lung tissues of PIE group were higher than those of Control group. We further verified the induction of PIE on macrophage polarization, as evidenced by the elevations of mRNA encoding M2 macrophage markers including Arg-1, CD206 (Mrc1) and cytokines including IL-6, IL-10, TNF-β1, CCL22, and VEGFA in pups of LPS-treated mothers. In vitro, flow cytometry determined that the PIE treatment increased the percentage of CD163+CD206+ cells in the sorted TAMs. Importantly, endoplasmic reticulum (ER) stress-markers (GRP78/BIP and CHOP), p-IRE1α, XBP1s, and PD-L1 were up-regulated in TAMs from PIE group. ER-stress inhibitor (KIRA6) not only reduced the levels of p-IRE1α and XBP1s, but also reverse the M2-like TAMs polarization and metastasis induced by PIE. In conclusion, the current study provides the evidences that IRE1α/XBP1-mediated M2-like TAMs polarization releases the pro-tumorigenic cytokines and PD-L1 expression, which may be a key regulatory mechanism of accelerating lung cancer in offspring of pregnancy mice exposed to LPS."}}]},{"typeName":"subject","multiple":true,"typeClass":"controlledVocabulary","value":["Medicine, Health and Life Sciences"]},{"typeName":"depositor","multiple":false,"typeClass":"primitive","value":"Ma Jingbo"},{"typeName":"dateOfDeposit","multiple":false,"typeClass":"primitive","value":"2023-08-24"}]}},"files":[{"label":"rawdata.xlsx","restricted":false,"version":1,"datasetVersionId":349429,"dataFile":{"id":7337650,"persistentId":"","filename":"rawdata.xlsx","contentType":"application/vnd.openxmlformats-officedocument.spreadsheetml.sheet","friendlyType":"MS Excel Spreadsheet","filesize":57992,"storageIdentifier":"s3://dvn-cloud:18a26fb1e26-26eeb740cfc4","rootDataFileId":-1,"md5":"06e77d805962bc777e013714666632df","checksum":{"type":"MD5","value":"06e77d805962bc777e013714666632df"},"tabularData":false,"creationDate":"2023-08-24","publicationDate":"2023-08-24","fileAccessRequest":true}}],"citation":"Ma Jingbo, 2023, \"Prenatal inflammation exposure accelerates lung cancer tumorigenesis in offspring mouse: possible links to IRE1α/XBP1-mediated M2-like polarization of TAMs and PD-L1 up-expression\", https://doi.org/10.7910/DVN/AG0A1Q, Harvard Dataverse, V1"}}