Diverse and divergent functions of IL-32β and IL-32γ isoforms in the regulation of malignant pleural mesothelioma cell growth and the production of VEGF-A and CXCL8

Muneo Numasaki; Koyu Ito; Kiyoshi Takagi; Kengo Nagashima; Hirotsugu Notsuda; Hirokazu Ogino; Rika Ando; Yoshihisa Tomioka; Takashi Suzuki; Yoshinori Okada; Yasuhiko Nishioka; Michiaki Unno

doi:10.1016/j.cellimm.2022.104652

Diverse and divergent functions of IL-32β and IL-32γ isoforms in the regulation of malignant pleural mesothelioma cell growth and the production of VEGF-A and CXCL8

Cell Immunol. 2023 Jan:383:104652. doi: 10.1016/j.cellimm.2022.104652. Epub 2022 Nov 30.

Authors

Affiliations

¹ 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.
² Department of Immunology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Miyagi, Japan.
³ Department of Pathology and Histotechnology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
⁴ Biostatistics Unit, Clinical and Translational Research Center, Keio University Hospital, Tokyo, Tokyo, Japan.
⁵ Department of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Miyagi, Japan.
⁶ Department of Respiratory Medicine and Rheumatology, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Tokushima, Japan.
⁷ Department of Nursing, Faculty of Medical Science and Welfare, Tohoku Bunka Gakuen University, Sendai, Miyagi, Japan.
⁸ Laboratory of Oncology, Pharmacy Practice and Sciences, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Miyagi, Japan.
⁹ Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.

PMID: 36516653
DOI: 10.1016/j.cellimm.2022.104652

Abstract

In this study, we sought to elucidate the roles of the interleukin (IL)-32β and IL-32γ 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-32γ resulted in enhanced IL-32β expression, which facilitated or suppressed the in vitro growth, and VEGF-A and CXCL8 expression. Overexpressed IL-32β-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-32β-deceased growth was mediated through mitogen-activated protein kinase (MAPK) pathway. NCI-H2373IL-32γ 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.

Keywords: CXCL8; IL-17A; IL-32; Malignant pleural mesothelioma; VEGF-A.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Humans
Interleukin-8* / metabolism
Interleukins* / genetics
Interleukins* / metabolism
Mesothelioma, Malignant* / metabolism
Mesothelioma, Malignant* / pathology
Protein Isoforms / metabolism
Vascular Endothelial Growth Factor A* / genetics
Vascular Endothelial Growth Factor A* / metabolism

Substances

Interleukins
Protein Isoforms
Vascular Endothelial Growth Factor A
IL32G protein, human
IL32 protein, human
CXCL8 protein, human
Interleukin-8