Effects of pepsin and pepstatin on reflux tonsil hypertrophy in vitro

Abstract

There is evidence that pepsin can aggravate tonsil hypertrophy. Pepstatin is a potent inhibitor of pepsin activity and could protect patients against reflux tonsil hypertrophy by inhibiting pepsin. We examined the effects of pepstatin on the development of tonsil hypertrophy to investigate pepsin’s role in the pathogenesis of tonsil lesions. We investigated whether pepstatin suppresses pepsin-mediated lymphocyte proliferation in tonsil hypertrophy. Forty-nine children with tonsil hypertrophy and twenty-two adults with tonsillitis were recruited to the study prior to surgery. Tonsil tissue from each patient was harvested and assessed for changes in the number of lymphocytes and macrophages in the presence of pepsin and pepstatin. We found that the proportions of CD4- and CD14-positive cells were significantly lower (p < 0.05), but that the proportions of CD19- and CD68-positive cells were significantly higher (p < 0.05), in children than in adults. There were significantly more CD4-positive cells after pepsin treatment, but these numbers were reduced by pepstatin. The levels of both interleukin-2 (IL-2) and interferon gamma (IFN-γ) increased significantly in response to pepsin, but were reduced when pepsin was inhibited by pepstatin. The level of IL-10 is reduced in pepsin-treated CD4 cells and the level is restored by pepstatin. IL-2 blocking reduced the increased CD4 cell number by pepsin. But, an additive or a synergic effect is not founded in combined with IL-2 blocking and pepstatin. Pepsin-positive cells did not co-localize with CD20 and CD45 cells, but they were found surrounding CD20- and CD45-positive hypertrophic tonsil cells. Pepsin-positive cells co-localized with CD68-positive cells. It is probable that pepsin from extraesophageal reflux aggravates tonsil hypertrophy and pepstatin exerts a protective effect by inhibiting pepsin activity.

Predictive Pediatric Characteristics for Revision Tonsillectomy After Intracapsular Tonsillectomy

“…25 An in vitro study concluded that pepsin likely aggravates tonsil hypertrophy in the context of GERD, although there is no direct evidence of this association. 26 Further research is required to determine the strength and cause of the GERD association with revision surgery risk. Recurrent or chronic tonsillitis was the most common diagnosis prompting revision surgery in our cohort.…”

Pepsin promotes IL-8 signaling-induced epithelial–mesenchymal transition in laryngeal carcinoma

“…Furthermore, pepstatin is well known to be an inhibitor of aspartic proteinases such as pepsin, cathepsins D and E [ 55 ]. Kim observed that pepsin from extraesophageal reflux aggravates tonsil hypertrophy and pepstatin exerts a protective effect by inhibiting pepsin activity [ 56 ]. Our results showed that IL-8 level was reduced when pepsin was inhibited by pepstatin; this coincided with significant upregulation of epithelial markers and downregulation of mesenchymal markers.…”

Effects of acids, pepsin, bile acids, and trypsin on laryngopharyngeal reflux diseases: physiopathology and therapeutic targets

“…Pepsin not only damages the laryngopharyngeal mucosa but also induces chronic inflammation of the surrounding tissues to cause vocal fold polyp [37], tonsillar hypertrophy [38,39], otitis media [40], recurrent respiratory papillomatosis [22,41], laryngopharyngeal tumors [34,36] and other diseases.…”