ABSTRACT
Objective: Neutrophils have an important role in the rapid innate immune response, and the release or active secretion of elastase from neutrophils is linked to various inflammatory responses. Purpose of this study was to determine how the human neutrophil elastase affects the interleukin-10 [IL-10] response in peripheral blood mononuclear cells [PBMC]
Materials and Methods: In this prospective study, changes in IL-10 messenger RNA [mRNA] and protein expression levels in monocytes derived from human PBMCs were investigated after stimulation with human neutrophil elastase [HNE]. A set of inhibitors was used for examining the pathways for IL-10 production induced by HNE
Results: Reverse transcription polymerase chain reaction [RT-PCR] showed that stimulation with HNE upregulated IL-10 mRNA expression by monocytes, while the enzyme-linked immunosorbent assay [ELISA] revealed an increase of IL-10 protein level in the culture medium. A phospholipase C inhibitor [U73122] partially blunted the induction of IL-10 mRNA expression by HNE, while IL-10 mRNA expression was significantly reduced by a protein kinase C [PKC] inhibitor [Rottlerin]. A calcium chelator [3,4,5-trimethoxybenzoic acid 8-[diethylamino]octyl ester: TMB-8] inhibited the response of IL-10 mRNA to stimulation by HNE. In addition, pretreatment with a broad-spectrum PKC inhibitor [Ro-318425] partly blocked the response to HNE. Finally, an inhibitor of PKC theta/delta abolished the increased level of IL-10 mRNA Expression
Conclusion: These results indicate that HNE mainly upregulates IL-10 mRNA expression and protein production in moncytes via a novel PKC theta/delta, although partially via the conventional PKC pathway
ABSTRACT
PURPOSE: To analyze unusual events and focus discussion on pulmonary metastasis in particular after low-dose-rate brachytherapy (LDR-BT) for prostate cancer (PCa). MATERIALS AND METHODS: A total of 616 consecutive patients who had undergone LDR-BT for clinically localized PCa at Jikei University Hospital between October 2003 and April 2010 were enrolled in this study. Follow-up information was summarized, and patterns of biochemical recurrence and clinical outcome were investigated. RESULTS: Disease risk was stratified as low-risk in 231 patients, intermediate-risk in 365, and high-risk in 20, respectively. Of these patients, 269 (43.7%) had received hormonal therapy (HT) in combination with LDR-BT, and 80 (13.0%) had received external beam radiotherapy (EBRT). Average dosimetric parameter values with and without EBRT were 95.3% and 94.2% for V100, 132.8 Gy and 164.2 Gy for D90, and 180.6 Gy2 and 173.7 Gy2 for the biologically effective dose. Biochemical recurrence was noted in 14 patients (6.1%) in the low-risk group, 25 patients (6.8%) in the intermediate-risk group, and 6 patients (30.0%) in the high-risk group, respectively. In these cases of biochemical recurrence, 9 (64.3%), 13 (52.0%), and 4 patients (66.7%) in each respective risk group showed signs of clinical recurrence. Five patients (19.2%) with clinical recurrence developed pulmonary metastases, of which 4 were isolated lesions. All tumors responded favorably to subsequent HT. CONCLUSIONS: LDR-BT for biologically aggressive PCa may be linked to possible pulmonary metastasis owing to tumor dissemination during seed implantation. This information is important in planning adequate treatment for these patients.