Histone acetyltransferase 1 up regulates Bcl2L12 expression in nasopharyngeal cancer cells.

The deregulation of Bcl2L12 expression in cancer has been recognized, but the causative factors are unknown. Histone acetyltransferases (HAT) play critical roles in the regulation gene transcription. This study tests a hypothesis that the aberrant activities of HAT induce deregulation of Bcl2L12 in nasopharyngeal cancer (NPC). In this study, human NPC tissues were collected from the clinic. The expression of Bcl2L12 and HATs in NPC cells was analyzed by real time RT-PCR and Western blotting. NPC cell apoptosis was analyzed by flow cytometry. The results showed that by screening the subtypes of HAT, the levels of HAT1 were uniquely higher in NPC as compared with non-cancer nasopharyngeal tissue. The levels of Bcl2L12 in NPC cells were positively correlated with HAT1. HAT1 involved in the STAT5 binding to the Bcl2L12 promoter. HAT1 increased the expression of Bcl2L12. Bcl2L12 mediated the effects of HAT1 on suppressing NPC cell apoptosis. Absorption of the HAT1 shRNA plasmid-carrying liposomes induced NPC cell apoptosis. In conclusion, inhibition of HAT1 can induce NPC cell apoptosis via increasing Bcl2L12 expression, which can be a potential therapy for NPC treatment.

Inhibition of Bcl2L12 Attenuates Eosinophilia-Related Inflammation in the Heart.

Background: The eosinophilic inflammation plays a critical role in myocarditis (Mcd); its underlying mechanism remains to be further elucidated. This study aims to investigate the role of Bcl2-like protein 12 (Bcl2L12) in inducing the defects of apoptosis in eosinophils (Eos) of the heart tissues. Methods: Human explant heart samples were collected. Eosinophilia and myocarditis (Mcd)-like inflammation were induced in the mouse heart by immunizing with murine cardiac α-myosin heavy chain (MyHCα) peptides. Results: Markedly more Eos were observed in heart tissues from patients with Mcd than those from patients with dilated cardiomyopathy. Eos isolated from Mcd hearts showed the signs of apoptosis defects. The Eo counts in the Mcd heart tissues were positively correlated with the Bcl2L12 expression in Eos isolated from the heart tissues. Exposure to interleukin 5 in the culture induced the expression of Bcl2L12 in Eos. Bcl2L12 bound c-Myc, the transcription factor of Fas ligand (FasL), to prevent c-Myc from binding to the FasL promoter, to restrict the FasL gene transcription in Eos. Inhibition of Bcl2L12 prevented the induction of eosinophilia and Mcd-like inflammation in the mouse heart. Conclusions: The Bcl2L12 expression contributes to apoptosis defects in Eos of the Mcd heart. Blocking Bcl2L12 prevents the eosinophilia induction and alleviates Mcd-like inflammation in mice.

Inhibition of squamous cancer growth in a mouse model by Staphylococcal enterotoxin B-triggered Th9 cell expansion.

Currently, therapy for squamous cancer (SqC) is unsatisfactory. Staphylococcal enterotoxin B (SEB) has strong immune regulatory activity. This study tests the hypothesis that SEB enforces the effect of immunotherapy on SqC growth in a mouse model. C3H/HeN mice and the SqC cell line squamous cell carcinoma VII were used to create an SqC mouse model. Immune cell assessment was performed by flow cytometry. Real-time RT-PCR and western blotting were used to evaluate target molecule expression. An apoptosis assay was used to assess the suppressive effect of T helper-9 (Th9) cells on the SqC cells. The results showed that immunotherapy consisting of SEB plus SqC antigen significantly inhibited SqC growth in the mice. The frequency of Th9 cells was markedly increased in the SqC tissue and mouse spleens after treatment. SEB markedly increased the levels of signal transducer and activator of transcription 5 phosphorylation and the expression of histone deacetylase-1 (HDAC1) and PU.1 (the transcription factor of the interleukin 9 (IL-9) gene) in CD4+ T cells. Exposure to SqC-specific Th9 cells markedly induced SqC cell apoptosis both in vitro and in vivo. In conclusion, the administration of SEB induces Th9 cells in SqC-bearing mice, and theseTh9 cells inhibit SqC growth.

Combination of specific allergen and probiotics induces specific regulatory B cells and enhances specific immunotherapy effect on allergic rhinitis.

The therapeutic efficacy of allergen specific immunotherapy (SIT) on allergic diseases is to be improved. Probiotics can regulate immune response. This study aims to promote the effect of SIT on allergic rhinitis (AR) by co-administration with Clostridium butyricum (Cb). In this study, patients with AR sensitized to mite allergens were enrolled to this study, and treated with SIT or/and Cb. The therapeutic efficacy was evaluated by the total nasal symptom scores (NSS), medication scores, serum specific IgE levels and T helper (Th)2 cytokine levels. The improvement of immune regulation in the AR patients was assessed by immunologic approaches. The results showed that treating AR patients with SIT alone markedly reduced NSS and medication scores; but did not alter the serum specific IgE, Th2 cytokines and skin prick test (SPT) index. The clinical symptoms on AR in SIT group relapsed one month after stopping SIT. Co-administration of Cb significantly enhanced the efficacy of SIT on AR as shown by suppression of NSS, medication scores, serum specific IgE, Th2 cytokines and SPT index; the regulatory B cell frequency was also markedly increased. Such an effect on AR was maintained throughout the observation period even after stopping the treatment. Butyrate blocked the activation of histone deacetylase-1, the downstream activities of epsilon chain promoter activation, and the IgE production in the antigen specific B cells. On the other hand, butyrate induced the IL-10 expression in B cells with a premise of the B cell receptor activation by specific antigens. In conclusion, administration with Cb can markedly enhance the efficacy of SIT on AR.

Nasopharyngeal cancer-derived microRNA-21 promotes immune suppressive B cells.

The prevalence of nasopharyngeal cancer (NPC) is high in the southern area of China and some other districts in the world. The pathogenesis of NPC is unclear. It is reported that some microRNAs (miR) are involved in the progression of NPC. This study aims to investigate the role of miR-21 in the induction of immune tolerance of NPC. In this study, NPC tissue was collected from patients with NPC. Assessment of miR was performed with real time quantitative RT-PCR. Western blotting was used to assess proteins of interleukin 10 and nuclear factor I-A (NFI-A). Immune cells were analyzed by flow cytometry. The results showed that NPC cell line C666-1 and surgically removed NPC tissue expressed miR-21, which was upregulated by the presence of the Toll-like receptor 3 ligand, Poly I: C. Exposure to miR-21 increased the expression of NFI-A and interleukin (IL)-10 in naive B cells. High frequency of IL-10(+) B cells was detected in the NPC tissue. The NPC- or miR-21-primed B cells suppressed cytotoxic CD8(+) T cell activities. We conclude that NPC-derived miR-21 induces IL-10(+) B cells; the latter is capable of suppressing CD8(+) T-cell activities. miR-21 may be a potential target in the treatment of NPC.