Antitumor activity of IL-32β through the activation of lymphocytes, and the inactivation of NF-κB and STAT3 signals

Abstract

Cytokine and activation of lymphocytes are critical for tumor growth. We investigated whether interleukin (IL)-32β overexpression changes other cytokine levels and activates cytotoxic lymphocyte, and thus modify tumor growth. Herein, IL-32β inhibited B16 melanoma growth in IL-32β-overexpressing transgenic mice (IL-32β mice), and downregulated the expressions of anti-apoptotic proteins (bcl-2, IAP, and XIAP) and cell growth regulatory proteins (Ki-67 antigen (Ki-67) and proliferating cell nuclear antigen (PCNA)), but upregulated the expressions of pro-apoptotic proteins (bax, cleaved caspase-3, and cleaved caspase-9). IL-32β also inhibited colon and prostate tumor growth in athymic nude mice inoculated with IL-32β-transfected SW620 colon or PC3 prostate cancer cells. The forced expression of IL-32β also inhibited cell growth in cultured colon and prostate cancer cells, and these inhibitory effects were abolished by IL-32 small interfering RNA (siRNA). IL-10 levels were elevated, but IL-1β, IL-6, and tumor necrosis factor-alpha (TNF-α) levels were reduced in the tumor tissues and spleens of IL-32β mice, and athymic nude mice. The number of cytotoxic T (CD8+) and natural killer (NK) cells in tumor tissues, spleen, and blood was significantly elevated in IL-32β mice and athymic nude mice inoculated with IL-32β-transfected cancer cells. Constituted activated NF-κB and STAT3 levels were reduced in the tumor tissues of IL-32β mice and athymic nude mice, as well as in IL-32β-transfected cultured cancer cells. These findings suggest that IL-32β inhibits tumor growth by increasing cytotoxic lymphocyte numbers, and by inactivating the NF-κB and STAT3 pathways through changing of cytokine levels in tumor tissues.

Interleukin-32α Inhibits Endothelial Inflammation, Vascular Smooth Muscle Cell Activation, and Atherosclerosis by Upregulating Timp3 and Reck through suppressing microRNA-205 Biogenesis

“…In previous studies, we also demonstrated an inhibitory role of the IL-32 isoforms (α, β, γ) in inflammatory diseases 19, 21, cancer 61, 62, 64, 65, and liver damage 18, 23. Interestingly, a previous study suggested a paradoxical dual function of IL-32γ in colitis 66.…”

The Rest of Interleukins

“…Yun et al (2013) demonstrated that IL-32 inhibits tumor growth through the increase in the number of cytotoxic lymphocytes. Yun et al (2013) demonstrated that IL-32 inhibits tumor growth through the increase in the number of cytotoxic lymphocytes.…”

Interleukin‐32β ameliorates metabolic disorder and liver damage in mice fed high‐fat diet

“…Finally, HFD promoted pro‐inflammatory cytokines such as IL‐1β, IL‐6, and TNF‐α in mouse liver, but did not promote other cytokines such as IL‐4, IL‐10, IL‐11, IL‐13, IL‐15, and IFN‐γ . We previously reported that IL‐32β showed antitumor activity in IL‐32β mice and modulated the levels of cytokines such as IL‐6, TNF‐α, IL‐1β, and IL‐10 . Kang et al reported that IL‐32β promotes the production of IL‐10, which is an anti‐inflammatory cytokine in human myeloid cells .…”