Some Macrophages With High Expression of CHOP Undergo Necroptosis in Chronic Rhinosinusitis.

BACKGROUND: Endoplasmic reticulum stress (ER stress) is activated in chronic sinusitis with nasal polyps (CRSwNP) and leads to increased expression of C/EBP homologous protein (CHOP). However, the role of CHOP in the pathogenesis of CRSwNP remains unclear.

METHODS: CHOP expression was detected by immunohistochemistry staining in nasal mucosa of control and CRSwNP patients. Co-localization of CHOP and cleaved caspase3, p-MLKL, and CD68 was detected by immunofluorescence staining in CRSwNP patients. TNFα, IFNγ, IL1β, LPS, and tunicamycin were added to primary dispersed nasal polyp cells (DNPCs) to explore their roles in cell death. Western blot, CCK8 assay, and flow cytometry were employed to detect cell death.

RESULTS: CHOP was specifically activated in CRSwNP compared to controls. It was mainly macrophages that highly expressed CHOP, some of which underwent apoptosis and the other underwent necroptosis. IL1β induced increased CHOP and apoptosis, and a slight p-MLKL. In addition, ER stress could also promote p-MLKL expression. Whereas classical TNFα plus IFNγ and LPS did not induce increased necroptosis in DNPCs.

CONCLUSION: IL1β induced the apoptotic pathway and minor necroptosis. And ER stress also plays a role in the occurrence of necroptosis in CRSwNP.