PMID- 31121496 OWN - NLM STAT- MEDLINE DCOM- 20200818 LR - 20200818 IS - 1096-0023 (Electronic) IS - 1043-4666 (Linking) VI - 120 DP - 2019 Aug TI - Cytokine expression profiles in cervical mucus from patients with cervical cancer and its precursor lesions. PG - 210-219 LID - S1043-4666(19)30129-2 [pii] LID - 10.1016/j.cyto.2019.05.011 [doi] AB - Human papillomavirus (HPV) infection can persist in the cervical epithelium without provoking a strong host immune response, leading to the development of cervical cancer. Cytokines, which mediate innate and adaptive immune activities, are secreted in the cervical mucus; however, there is currently no appropriate method for assessing cytokine levels in mucus specimens. Here, we employed multiplexed bead-based immunoassays to examine cytokine levels in cervical mucus using both weighted-volume and total protein concentration methods to adjust for different specimen volumes in individual patients. Out of 18 cytokines initially examined in the primary cohort patient group (n = 28), 14 were detected in more than 10% of the samples. Of these 14 cytokines, expression levels of interferon (IFN)-gamma, granulocyte-macrophage colony-stimulating factor (GM-CSF), RANTES, and eotaxin were significantly increased with the disease severity in the secondary cohort patient group (n = 235). We also examined associations between cytokine levels and clinical parameters, such as cytology and HPV genotype. Of the 14 cytokines, granulocyte colony-stimulating factor (G-CSF) was downregulated in HPV-positive specimens. Examination of co-expression patterns of cytokines in relation to HPV infection status revealed that several pairs of cytokines were simultaneously upregulated in HPV-positive cases, including INF-gamma and interleukin (IL)-17A, GM-CSF and monocyte chemoattractant protein-1 (MCP-1), GM-CSF and RANTES, IL-17A and RANTES, and MCP-1 and eotaxin. Interestingly, upregulation of GM-CSF and RANTES might reflect a shift in immuno-regulatory cytokines in HPV-positive specimens, potentially associated with more severe cervical neoplasia. CI - Copyright (c) 2019 The Authors. Published by Elsevier Ltd.. All rights reserved. FAU - Otani, Sayaka AU - Otani S AD - Department of Obstetrics and Gynecology, Fujita Health University, School of Medicine, 1-98, Dengakugakubo, Kutsukakecho, Toyoake, Aichi 470-1192, Japan. FAU - Fujii, Takuma AU - Fujii T AD - Department of Obstetrics and Gynecology, Fujita Health University, School of Medicine, 1-98, Dengakugakubo, Kutsukakecho, Toyoake, Aichi 470-1192, Japan. Electronic address: fujiit44@fujita-hu.ac.jp. FAU - Kukimoto, Iwao AU - Kukimoto I AD - Pathogen Genomics Center, National Institute of Infectious Diseases, 4-7-1, Gakuen, Musashi-murayama, Tokyo 208-0011, Japan. FAU - Yamamoto, Naoki AU - Yamamoto N AD - Regenerative Medicine Support Promotion Facility, Center for Research Promotion and Support, Fujita Health University, School of Medicine, 1-98, Dengakugakubo, Kutsukakecho, Toyoake, Aichi 470-1192, Japan. FAU - Tsukamoto, Tetsuya AU - Tsukamoto T AD - Department of Pathology, Fujita Health University, School of Medicine, 1-98, Dengakugakubo, Kutsukakecho, Toyoake, Aichi 470-1192, Japan. FAU - Ichikawa, Ryoko AU - Ichikawa R AD - Department of Obstetrics and Gynecology, Fujita Health University, School of Medicine, 1-98, Dengakugakubo, Kutsukakecho, Toyoake, Aichi 470-1192, Japan. FAU - Nishio, Eiji AU - Nishio E AD - Department of Obstetrics and Gynecology, Fujita Health University, School of Medicine, 1-98, Dengakugakubo, Kutsukakecho, Toyoake, Aichi 470-1192, Japan. FAU - Iwata, Aya AU - Iwata A AD - Department of Obstetrics and Gynecology, Fujita Health University, School of Medicine, 1-98, Dengakugakubo, Kutsukakecho, Toyoake, Aichi 470-1192, Japan. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190520 PL - England TA - Cytokine JT - Cytokine JID - 9005353 RN - 0 (Cytokines) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Cell Line, Tumor MH - Cervix Mucus/*metabolism MH - Cohort Studies MH - Cytokines/*metabolism MH - Female MH - Humans MH - Middle Aged MH - Papillomavirus Infections/metabolism/virology MH - Precancerous Conditions/*metabolism/virology MH - Severity of Illness Index MH - Uterine Cervical Neoplasms/*metabolism/virology MH - Young Adult OTO - NOTNLM OT - Cervix OT - Chemokine OT - Immune response OT - Papillomavirus EDAT- 2019/05/24 06:00 MHDA- 2020/08/19 06:00 CRDT- 2019/05/24 06:00 PHST- 2018/10/30 00:00 [received] PHST- 2019/05/13 00:00 [revised] PHST- 2019/05/13 00:00 [accepted] PHST- 2019/05/24 06:00 [pubmed] PHST- 2020/08/19 06:00 [medline] PHST- 2019/05/24 06:00 [entrez] AID - S1043-4666(19)30129-2 [pii] AID - 10.1016/j.cyto.2019.05.011 [doi] PST - ppublish SO - Cytokine. 2019 Aug;120:210-219. doi: 10.1016/j.cyto.2019.05.011. Epub 2019 May 20.