RESUMO
BACKGROUND: The developing field of osteoimmunology supports importance of an interferon (IFN) response pathway in osteoblasts. Clarifying osteoblast-IFN interactions is important because IFN is used as salvage anti-tumor therapy but systemic toxicity is high with variable clinical results. In addition, osteoblast response to systemic bursts and disruptions of IFN pathways induced by viral infection may influence bone remodeling. ZIKA virus (ZIKV) infection impacts bone development in humans and IFN response in vitro. Consistently, initial evidence of permissivity to ZIKV has been reported in human osteoblasts. HYPOTHESIS: Osteoblast-like Saos-2 cells are permissive to ZIKV and responsive to IFN. METHODS: Multiple approaches were used to assess whether Saos-2 cells are permissive to ZIKV infection and exhibit IFN-mediated ZIKV suppression. Proteomic methods were used to evaluate impact of ZIKV and IFN on Saos-2 cells. RESULTS: Evidence is presented confirming Saos-2 cells are permissive to ZIKV and support IFN-mediated suppression of ZIKV. ZIKV and IFN differentially impact the Saos-2 proteome, exemplified by HELZ2 protein which is upregulated by IFN but non responsive to ZIKV. Both ZIKV and IFN suppress proteins associated with microcephaly/pseudo-TORCH syndrome (BI1, KI20A and UBP18), and ZIKV induces potential entry factor PLVAP. CONCLUSIONS: Transient ZIKV infection influences osteoimmune state, and IFN and ZIKV activate distinct proteomes in Saos-2 cells, which could inform therapeutic, engineered, disruptions.
Assuntos
Antivirais/imunologia , Interferon Tipo I/imunologia , Osteoblastos/imunologia , Infecção por Zika virus/imunologia , Zika virus/imunologia , Animais , Antivirais/farmacologia , Linhagem Celular Tumoral , Chlorocebus aethiops , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/imunologia , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Interações Hospedeiro-Patógeno/imunologia , Humanos , Interferon Tipo I/farmacologia , Camundongos Knockout , Osteoblastos/metabolismo , Osteoblastos/virologia , Proteoma/imunologia , Proteoma/metabolismo , Proteômica/métodos , Células Vero , Replicação Viral/efeitos dos fármacos , Replicação Viral/imunologia , Zika virus/fisiologia , Infecção por Zika virus/metabolismo , Infecção por Zika virus/virologiaRESUMO
<p><b>OBJECTIVE</b>To evaluate the efficacy of Bawu Decoction (, BWD, Palmul-tang in Korean) against benign prostatic hyperplasia (BPH).</p><p><b>METHODS</b>Twenty-four male Wistar rats were divided into 4 groups, with 6 rats in each group. The 4 study groups included sham-operated group (CON), BPH model group, fifinasteride-treated group, and BWD-treated group. All the groups except CON group received a subcutaneous injection of 10 mg/kg of testosterone, while CON group received saline. Finasteride at a dose of 5 mg/kg was administered to the finasteride-treated group for a period of 4 weeks. BWD group received BWD at a dose of 200 mg/kg for 4 weeks. The prostatic weight, prostate weight to body weight ratio, relative prostate weight ratio, serum testosterone and dihydrotestosterone (DHT) level, and histological analysis of prostatic tissue were analyzed.</p><p><b>RESULTS</b>Compared to BPH model group, BWD administration was associated with reductions in prostatic weight, prostate and relative prostate weight ratio weight to body weight ratio (P<0.05). The concentration of serum testosterone and DHT were higher in BPH group compared with CON group (P<0.05). Administration of finasteride and BWD suppressed the elevation of serum testosterone and DHT levels signifificantly (both P<0.05). In addition, BWD suppressed the growth of prostatic tissue (P<0.05).</p><p><b>CONCLUSION</b>BWD has suppressant effects on development of BPH through inhibition of serum testosterone and DHT.</p>
