RESUMO
Studies have demonstrated that the anti-tumour effect of natural killer (NK) cells is successful for patients with several cancers. Although interleukin-32 (IL-32) is endogenously expressed in NK cells, cytolytic function of NK cells against cancer cells has not been fully demonstrated. In the present study, we found that the growth of cancer cells was suppressed when colon cancer cells or prostate cancer cells were co-cultured with NK-92 cells, an NK cell line. We also found that the expression of tumour necrosis factor receptor 2 and death receptor 3 (DR3) was increased in PC3 cells, and the expression of FAS and DR3 was increased in SW620 cells by co-culture with NK-92 cells. However, cancer cell growth inhibition and IL-32 expression were abolished when cancer cells were co-cultured with NK cells transfected with small interfering (si) RNA of IL-32. DR3 expression was also diminished by co-culture with IL-32-specific siRNA-transfected NK-92 cells. Expression of APO3L, a ligand of DR3, was elevated in NK cells that were co-cultured with cancer cells. It was also found that expression of apoptosis-related proteins such as cleaved caspase-3 and bax was increased in cancer cells co-cultured with NK-92 cells, but their expression was abolished by co-culture with IL-32 siRNA-transfected NK-92 cells. Moreover, knockdown of DR3 in co-culture of NK-92 cells with cancer cells by siRNA or antibodies of DR3 and APO3L reversed the growth inhibitory effect of NK-92 cells. In conclusion, our study showed that IL-32 enhanced the cytotoxic effect of NK-92 cells on the cancer cells through activation of DR3 and caspase-3.
Assuntos
Interleucinas/imunologia , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/imunologia , Membro 25 de Receptores de Fatores de Necrose Tumoral/imunologia , Caspase 3/biossíntese , Caspase 3/imunologia , Linhagem Celular Tumoral , Técnicas de Cocultura , Proteína Ligante Fas/biossíntese , Proteína Ligante Fas/imunologia , Humanos , Interleucinas/antagonistas & inibidores , Masculino , RNA Interferente Pequeno/imunologia , RNA Interferente Pequeno/metabolismo , Membro 25 de Receptores de Fatores de Necrose Tumoral/biossíntese , Receptores Tipo II do Fator de Necrose Tumoral/imunologia , Proteína X Associada a bcl-2/biossínteseRESUMO
The oriental herbal combination allergina has been shown to inhibit allergic inflammation. In the present study, we demonstrate that the oral administration of allergina markedly inhibits the progression of inflammatory diseases, such as graft-versus-host diseases (in the allogeneic bone marrow transplantation and the parent-into-F1 transplantation models), collagen-induced arthritis and sheep red blood cell-induced delayed type hypersensitivity. The immunosuppressive activity of allergina in vivo appears to be associated, at least in part, with the inhibition of tumor necrosis factor-alpha production. In conclusion, our results suggest that allergina could be useful as a immunosuppressive agent for the treatment of macrophage-related inflammatory disease.