Damage-associated molecular patterns stimulate interleukin-33 expression in nasal polyp epithelial cells

Area of Science:

• Immunology
• Otolaryngology
• Molecular Biology

Background:

• Chronic rhinosinusitis with nasal polyps (CRSwNP) involves eosinophilic inflammation and T-helper 2 (Th2) cytokine production.
• Innate lymphoid cells producing Th2 cytokines are found in nasal polyps and can be activated by interleukin-33 (IL-33).

Purpose of the Study:

• To investigate if tissue damage molecules, high mobility group box-1 (HMGB-1) and adenosine triphosphate (ATP), induce IL-33 expression in sinonasal epithelial cells (SNECs) from CRSwNP patients.

Main Methods:

• Ethmoid tissue from CRSwNP patients and controls was used for immunohistochemistry and SNEC culture.
• SNECs were exposed to HMGB-1 or ATP in vitro.
• IL-33 mRNA and protein levels were quantified using real-time PCR and immunocytochemistry.

Main Results:

• IL-33 expression in CRSwNP SNECs was altered, appearing in more apical cells and outside the nucleus.
• Exposure to HMGB-1 or ATP significantly increased IL-33 mRNA expression in SNECs from CRSwNP patients.
• Increased IL-33 mRNA levels correlated with increased protein levels.

Conclusions:

• Tissue damage acts as a nonspecific trigger for IL-33 production in the sinonasal epithelium of treatment-resistant CRSwNP.
• This mechanism may perpetuate eosinophilic inflammation and explain the role of various agents in CRSwNP exacerbations.