IL-10 Plays a Pivotal Role in Tamoxifen-Induced Spasmolytic Polypeptide-Expressing Metaplasia in Gastric Mucosa

ABSTRACT

BACKGROUND/AIMS: Gastric cancer evolves in the pathologic mucosal milieu, and its development is characterized by both the loss of acid-secreting parietal cells and mucosal cell metaplasia, called spasmolytic polypeptide-expressing metaplasia (SPEM). Cytokines, such as interleukin (IL)-10, IL-1β, and IL-6, play a key role in gastric carcinogenesis. However, changes in the cytokine profile of SPEM have not been evaluated. METHODS: To induce SPEM in mouse stomachs, C57BL/6 mice were intraperitoneally injected with tamoxifen and sacrificed at 3, 10, and 21 days after treatment. RNA-sequencing (RNA-seq) and a multiplex bead array were used to measure cytokines in the stomachs of tamoxifen-treated/control mice. RESULTS: The administration of tamoxifen led to the rapid development and histological normalization of SPEM 3 and 10 days after administration, respectively. RNA-seq revealed that the expression of IL-10 was decreased 3 days after tamoxifen administration. The multiplex assay identified a significant decline in IL-10 levels 3 days after tamoxifen treatment (58.38±34.44 pg/mL vs 94.09±4.98 pg/mL, p=0.031), which normalized at 10 and 21 days after tamoxifen treatment. Immunofluorescence staining confirmed that IL-10 expression was markedly decreased at the time of SPEM development and subsequently returned to normal, accompanied by a reversal in histologic changes. CONCLUSIONS: IL-10 may play a pivotal role in the tamoxifen-induced acute development of gastric SPEM.