Role of Th1-stimulating cytokines in bacillus Calmette–Guérin (BCG)-induced macrophage cytotoxicity against mouse bladder cancer MBT-2 cells

Abstract

SummaryPreviously, we have demonstrated that macrophages exhibited cytotoxicity toward mouse bladder cancer MBT-2 cells upon bacille Calmette-Guérin (BCG) stimulation. In this study, we have investigated the role of Th1-stimulating cytokines in BCG-induced macrophage cytotoxicity. Thioglycollate-elicited peritoneal exudate cells (PECs) were used as a conventional source for macrophages and the induction of PEC effector functions (cytolytic activity and cytokine production) by BCG was evaluated in vitro.

Immunomodulatory effects of recombinant BCG expressing MSP-1C ofPlasmodium falciparumon LPS- or LPS+IFN-γ-stimulated J774A.1 cells

“…We demonstrate here for the first time that the rBCG strain increased macrophage phagocytic activity and induced higher production of NO, iNOS, and pro-inflammatory cytokines such as TNF-α and IL-1β than those produced by parent BCG-infected macrophages. The results are consistent with our previous finding 39 and other studies [46][47][48][49][50] demonstrating that a recombinant BCG is more potent in activating macrophages than parental BCG. These findings support our previous data showing that the rBCG vaccine capable of inducing a strong cell mediated and humoral immune responses in animal model.…”

“…[42][43][44][45] Indeed, knowledge regarding the ability of a recombinant BCG to stimulate macrophage activation is well established. For example Luo et al 46 have demonstrated that a recombinant BCG expressing mouse IL-18 (rBCG-mIL-18) strain significantly increased macrophage cytotoxicity against bladder cancer MBT-2 cells and induced higher levels of IFN-γ and TNF-α in the culture supernatant of the cells than control BCG. Xu et al 47 also demonstrated that a recombinant BCG strain that secretes the chimeric protein of Ag85B and ESAT-6 (rBCG-A(N)-E-A(C)) induced higher expression levels of CD86, CD80, CD40, and HLA-DR as well as increased in TNF-α production of THP-1 cells.…”

Interleukin-10 inhibitsMycobacterium bovisbacillus Calmette–Guérin (BCG)-induced macrophage cytotoxicity against bladder cancer cells

“…Furthermore, both murine and human macrophages have been observed to produce a number of cytokines (e.g. TNF-a, IL-6 and IL-10) in response to BCG stimulation in vitro [20][21][22][23][24][25]. In addition to their function as antigen-presenting cells, macrophages can also act as cytostatic/cytotoxic effector cells against bladder cancer cells [4,6,[24][25][26][27][28].…”

“…TNF-a, IL-6 and IL-10) in response to BCG stimulation in vitro [20][21][22][23][24][25]. In addition to their function as antigen-presenting cells, macrophages can also act as cytostatic/cytotoxic effector cells against bladder cancer cells [4,6,[24][25][26][27][28]. Macrophages exert their tumoricidal activity through cell-cell contact and/or release of soluble cytotoxic effector molecules such as TNF-a and nitric oxide (NO) [6,[24][25][26][27][28].…”

“…In addition to their function as antigen-presenting cells, macrophages can also act as cytostatic/cytotoxic effector cells against bladder cancer cells [4,6,[24][25][26][27][28]. Macrophages exert their tumoricidal activity through cell-cell contact and/or release of soluble cytotoxic effector molecules such as TNF-a and nitric oxide (NO) [6,[24][25][26][27][28]. Both TNF-a and NO are known to induce cell death through the apoptotic pathways [29][30][31].…”