PMID- 36516653 OWN - NLM STAT- MEDLINE DCOM- 20230203 LR - 20230213 IS - 1090-2163 (Electronic) IS - 0008-8749 (Linking) VI - 383 DP - 2023 Jan TI - Diverse and divergent functions of IL-32beta and IL-32gamma isoforms in the regulation of malignant pleural mesothelioma cell growth and the production of VEGF-A and CXCL8. PG - 104652 LID - S0008-8749(22)00177-0 [pii] LID - 10.1016/j.cellimm.2022.104652 [doi] AB - In this study, we sought to elucidate the roles of the interleukin (IL)-32beta and IL-32gamma in mesothelioma cell growth, and vascular endothelial growth factor (VEGF)-A and C-X-C motif chemokine ligand 8 (CXCL8) expression. IL-32 elicited a growth-promoting effect against one of the six mesotheliomas lines and exerted diverse regulatory functions in VEGF-A and CXCL8 secretion from mesotheliomas stimulated with or without IL-17A. Retroviral-mediated transduction of mesothelioma lines with IL-32gamma resulted in enhanced IL-32beta expression, which facilitated or suppressed the in vitro growth, and VEGF-A and CXCL8 expression. Overexpressed IL-32beta-augmented growth and VEGF-A and CXCL8 production were mainly mediated through the phosphatidylinositol-3 kinase (PI3K) signaling pathway. On the other hand, overexpressed IL-32beta-deceased growth was mediated through mitogen-activated protein kinase (MAPK) pathway. NCI-H2373IL-32gamma tumors grew faster than NCI-H2373Neo tumors in a xenograft model, which was associated with increased vascularity. These findings indicate that IL-32 are involved in the regulation of growth and angiogenic factor production in mesotheliomas. CI - Copyright (c) 2022 Elsevier Inc. All rights reserved. FAU - Numasaki, Muneo AU - Numasaki M AD - Laboratory of Clinical Science and Biomedicine, Faculty of Pharmaceutical Sciences, Josai University, Sakado, Saitama, Japan; Department of Geriatrics and Gerontology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Miyagi, Japan; Department of Nursing, Faculty of Medical Science and Welfare, Tohoku Bunka Gakuen University, Sendai, Miyagi, Japan; Laboratory of Clinical Science and Biomedicine, Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama 350-0295, Japan. Electronic address: mnumasaki@ns.tbgu.ac.jp. FAU - Ito, Koyu AU - Ito K AD - Department of Immunology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Miyagi, Japan. FAU - Takagi, Kiyoshi AU - Takagi K AD - Department of Pathology and Histotechnology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan. FAU - Nagashima, Kengo AU - Nagashima K AD - Biostatistics Unit, Clinical and Translational Research Center, Keio University Hospital, Tokyo, Tokyo, Japan. FAU - Notsuda, Hirotsugu AU - Notsuda H AD - Department of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Miyagi, Japan. FAU - Ogino, Hirokazu AU - Ogino H AD - Department of Respiratory Medicine and Rheumatology, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Tokushima, Japan. FAU - Ando, Rika AU - Ando R AD - Department of Nursing, Faculty of Medical Science and Welfare, Tohoku Bunka Gakuen University, Sendai, Miyagi, Japan. FAU - Tomioka, Yoshihisa AU - Tomioka Y AD - Laboratory of Oncology, Pharmacy Practice and Sciences, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Miyagi, Japan. FAU - Suzuki, Takashi AU - Suzuki T AD - Department of Pathology and Histotechnology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan. FAU - Okada, Yoshinori AU - Okada Y AD - Department of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Miyagi, Japan. FAU - Nishioka, Yasuhiko AU - Nishioka Y AD - Department of Respiratory Medicine and Rheumatology, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Tokushima, Japan. FAU - Unno, Michiaki AU - Unno M AD - Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20221130 PL - Netherlands TA - Cell Immunol JT - Cellular immunology JID - 1246405 RN - 0 (Interleukins) RN - 0 (Protein Isoforms) RN - 0 (Vascular Endothelial Growth Factor A) RN - 0 (IL32G protein, human) RN - 0 (IL32 protein, human) RN - 0 (CXCL8 protein, human) RN - 0 (Interleukin-8) SB - IM MH - Humans MH - *Interleukins/genetics/metabolism MH - *Mesothelioma, Malignant/metabolism/pathology MH - Protein Isoforms/metabolism MH - *Vascular Endothelial Growth Factor A/genetics/metabolism MH - *Interleukin-8/metabolism OTO - NOTNLM OT - CXCL8 OT - IL-17A OT - IL-32 OT - Malignant pleural mesothelioma OT - VEGF-A COIS- Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2022/12/15 06:00 MHDA- 2023/01/11 06:00 CRDT- 2022/12/14 18:27 PHST- 2022/05/29 00:00 [received] PHST- 2022/11/23 00:00 [revised] PHST- 2022/11/27 00:00 [accepted] PHST- 2022/12/15 06:00 [pubmed] PHST- 2023/01/11 06:00 [medline] PHST- 2022/12/14 18:27 [entrez] AID - S0008-8749(22)00177-0 [pii] AID - 10.1016/j.cellimm.2022.104652 [doi] PST - ppublish SO - Cell Immunol. 2023 Jan;383:104652. doi: 10.1016/j.cellimm.2022.104652. Epub 2022 Nov 30.