Laryngopharyngeal Reflux Disease
Mechanism of pepsin promoting lingual tonsil hypertrophy by stimulating macrophage
Huang Lijun, Tan Jiajie, Peng Lingyi, Dai Yuanfeng, Lyu Zehong, Huang Xueqiong, Li Xiangping
Published 2022-10-07
Cite as Chin J Otorhinolaryngol Head Neck Surg, 2022, 57(10): 1203-1211. DOI: 10.3760/cma.j.cn115330-20220618-00358
Abstract
ObjectiveTo investigate the possible pathophysiological mechanism of laryngopharyngeal reflux (LPR) in the development of lingual tonsil hypertrophy (LTH).
MethodsThe lingual tonsil tissues were collected from 73 patients [48 males and 25 females, aged from 24 to 76 (52.86±12.04) years] who underwent surgery for laryngopharyngeal diseases at the Department of Otolaryngology and Head and Neck Surgery, Southern Hospital of Southern Medical University from October 2019 to December 2020, and the lingual tonsil grade (LTG), reflux symptom index (RSI) and reflux finding score (RFS) were assessed. The expression of pepsin in LTH was detected by immunohistochemistry. The coexpression of pepsin and macrophages were detected by immunohistofluorescence. In vitro, cytological experiments and pathway assays were performed on macrophages stimulated by pepsin. Pathway alterations of macrophages in pepsin-positive high-grade LTH were detected by double-fluorescence immunohistochemistry. Data were analyzed by SPSS 20.0 software.
ResultsThere were 44 clinically significant LPRD patients with LTG 3 and 4, and the pepsin positive rate was 88.6% (39/44). While, the pepsin positive rate of LTG 1 and 2 was 48.3% (14/29). LTG was significantly positively correlated with RFS/RSI positive rate(χ2=23.01/19.62, P<0.001/0.001; r=0.54/0.51, P<0.001/0.001) and pepsin tissue staining intensity (H=21.58, P<0.001; r=0.53, P<0.001), respectively. Pepsin and macrophages were clearly colocalized in high grade LTH. In vitro, pepsin promoted macrophage proliferation (P<0.05) and production of IL-6/IL-8 (P<0.05). Pepsin significantly up-regulated the p38/JNK MAPK pathway in macrophages (P<0.05). Pepsin up-regulated the expression of IL-6 and IL-8 of macrophages by activating the p38 MAPK pathway (P<0.05), and up-regulated the expression of IL-8 by activating the JNK pathway (P<0.05). The p38/JNK MAPK pathways were highly expressed in macrophages of pepsin-positive LTH (P<0.05).
ConclusionsLPR is an important pathogenic factor in LTH. Macrophages may mediate pepsin-induced inflammation and the pathogenesis of LTH.
Key words:
Lingual tonsil hypertrophy; Pepsin; Macrophage; Laryngopharyngeal reflux; Inflammation
Contributor Information
Huang Lijun
Department of Otorhinolaryngology-Head and Neck Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510000, China
Tan Jiajie
Department of Otorhinolaryngology-Head and Neck Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510000, China
Peng Lingyi
Department of Otorhinolaryngology-Head and Neck Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510000, China
Dai Yuanfeng
Department of Otorhinolaryngology-Head and Neck Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510000, China
Lyu Zehong
Department of Otorhinolaryngology-Head and Neck Surgery, Guangdong Provincial People′s Hospital, Guangzhou 510000, China
Huang Xueqiong
Department of Otorhinolaryngology-Head and Neck Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510000, China
Li Xiangping
Department of Otorhinolaryngology-Head and Neck Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510000, China
