Hong Sung-Moon, Park Il-Ho, Um Ji-Young, Shin Jae-Min, Lee Heung-Man
Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Korea University, Seoul, Korea.
Department of Biomedical Sciences, Korea University Graduate School, Korea University, Seoul, Korea.
Int Forum Allergy Rhinol. 2015 Oct;5(10):923-8. doi: 10.1002/alr.21555. Epub 2015 Jun 10.
Fibroblast migration is crucial for normal wound repair after sinonasal surgery. Histamine is known to be involved in wound healing by its effects on cell proliferation and migration. This study aimed to determine whether histamine affects the migration of nasal fibroblasts and to investigate the mechanism of action of histamine on nasal fibroblasts.
Primary cultures of nasal fibroblasts were established from inferior turbinate samples. Fibroblast migration was evaluated with scratch assays. Cells were treated with histamine and/or histamine receptor-selective antagonists. U-73122 and pertussis toxin, which are selective inhibitors of the lower signaling pathway of H1R and H4R, were used to confirm the modulation of nasal fibroblast migration by histamine. Fibroblast cytoskeletal structures were visualized with immunocytochemistry.
Histamine significantly stimulated the migration of nasal fibroblasts. Antagonists selective for HR1 and HR4 significantly reduced nasal fibroblast migration. In immunocytochemical staining, histamine treatment increased membrane ruffling and pyrilamine, diphenhydramine, fexofenadine, and JNJ7777120 decreased histamine-induced membrane ruffling. U-73122 and pertussis toxin also decreased histamine-induced migration of fibroblasts. Histamine maintains its stimulatory effects on fibroblast migration in the presence of mitomycin C, which blocks proliferation of cells.
We showed that histamine stimulates fibroblast migration in nasal fibroblasts. This effect appeared to be mediated by HR1 and HR4. However, because fibroblast migration also can be involved in scaring and fibrosis, more research is necessary to determine the effects of antihistamine on wound healing after sinus surgery.
成纤维细胞迁移对于鼻窦手术后的正常伤口修复至关重要。已知组胺通过其对细胞增殖和迁移的作用参与伤口愈合。本研究旨在确定组胺是否影响鼻成纤维细胞的迁移，并探讨组胺对鼻成纤维细胞的作用机制。
从下鼻甲样本中建立鼻成纤维细胞原代培养物。用划痕试验评估成纤维细胞迁移。细胞用组胺和/或组胺受体选择性拮抗剂处理。U-73122和百日咳毒素是H1R和H4R下游信号通路的选择性抑制剂，用于确认组胺对鼻成纤维细胞迁移的调节作用。用免疫细胞化学法观察成纤维细胞的细胞骨架结构。
组胺显著刺激鼻成纤维细胞的迁移。对HR1和HR4有选择性的拮抗剂显著降低鼻成纤维细胞的迁移。在免疫细胞化学染色中，组胺处理增加了膜皱褶，而吡苄明、苯海拉明、非索非那定和JNJ7777120减少了组胺诱导的膜皱褶。U-73122和百日咳毒素也降低了组胺诱导的成纤维细胞迁移。在丝裂霉素C存在的情况下，组胺对成纤维细胞迁移仍保持其刺激作用，丝裂霉素C可阻断细胞增殖。
我们表明组胺刺激鼻成纤维细胞的迁移。这种作用似乎是由HR1和HR4介导的。然而，由于成纤维细胞迁移也可能参与瘢痕形成和纤维化，因此需要更多的研究来确定抗组胺药对鼻窦手术后伤口愈合的影响。
