We previously reported that treatment with tricin (4’,5,7-trihydroxy-3’,5’-dimethoxyflavone) after human cytomegalovirus (HCMV) infection significantly suppressed both infectious virus production and HCMV replication in human embryonic lung fibroblast (HEL) cells. Moreover, we recently revealed that HCMV infection can increase the expression of CC-motif ligand 2 (CCL2/MCP-1) and CCR2, a specific receptor for CCL2, which can enhance HCMV infection and replication, in turn. In this study, we examined whether CCL2 and/or CCR2 are involved in the anti-HCMV effects of tricin in HEL cells. Exposure of fibroblasts to tricin inhibited infectious HCMV production, with concomitant decreases in CCL2 and CCR2 transcript levels and CCL2 protein levels in a dose-dependent manner. Propagermanium, an inhibitor of CCR2 function, has also been shown to inhibit infectious HCMV production with concomitant decreases in CCL2 protein levels. We further observed that tricin and propagermanium reduced mRNA expression of HCMV immediate early gene and DNA polymerase in a dose-dependent manner. These results suggest that tricin is a novel anti-inflammatory compound with potential anti-HCMV activity, and CCL2/CCR2 interactions are associated with HCMV replication.

Background/Aims: Mucosal adaptation of the ileum toward colonic epithelium has been reported in pouchitis in ulcerative colitis (UC); however, the clinical characteristics, endoscopic findings, and outcomes in patients with pouchitis with ileal mucosal adaptation are poorly understood. Methods: This was a single-center retrospective study comprising UC patients treated by proctocolectomy with ileal pouch-anal anastomosis who had undergone pouchoscopy at the University of Tsukuba Hospital between 2005 and 2022. Endoscopic phenotypes were evaluated according to the Chicago classification. High-iron diamine staining (HID) was performed to identify sulfomucin (colon-type mucin)-producing goblet cells (GCs) in pouch biopsies. We compared clinical data between patients with (high HID group) and without > 10% sulfomucin-producing GCs in at least one biopsy (low HID group). Results: We reviewed 390 endoscopic examination reports from 50 patients. Focal inflammation was the most common phenotype (78%). Five patients (10%) required diverting ileostomy. Diffuse inflammation and fistula were significant risk factors for diverting ileostomy. The median proportion of sulfomucin-producing GCs on histological analysis of 82 pouch biopsies from 23 patients was 9.9% (range, 0%–93%). The duration of disease was significantly greater in the high HID group compared to the low HID group. The median percentage of sulfomucin-producing GCs was significantly higher in patients with diffuse inflammation or fistula compared to other endoscopic phenotypes (14% vs. 6.0%, P= 0.011). Conclusions Greater proportions of sulfomucin-producing GCs were observed in endoscopic phenotypes associated with poor outcomes in UC, indicating patients with pouchitis showing colonic metaplasia of GCs may benefit from early interventions.