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.


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


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