Damage-associated molecular patterns stimulate interleukin-33 expression in nasal polyp epithelial cells
Funding sources for the study: NIH, National Institute of Allergy and Infectious Diseases (NIAID) (AI072502 to A.P.L.).
Potential conflict of interest: None provided.
Presented orally at the Annual ARS Meeting on September 8, 2012, Washington, DC.
Chronic rhinosinusitis with nasal polyps (CRSwNP) is a disorder characterized by eosinophilic inflammation and local T-helper 2 (Th2) cytokine production. Innate lymphoid cells that elaborate Th2 cytokines have recently been characterized within nasal polyps. These cells can be activated by the epithelial cell-derived cytokine interleukin-33 (IL-33). The objective of this study is to determine whether 2 molecules associated with tissue damage (high mobility group box-1 [HMGB-1] and adenosine triphosphate [ATP]) elicit expression of IL-33 in sinonasal epithelial cells (SNECs) derived from recalcitrant CRSwNP patients.
Ethmoid tissue was obtained from 8 recalcitrant CRSwNP and 9 control subjects during endoscopic sinus surgery (ESS). Tissue was prepared for immunohistochemistry and for SNEC air-liquid interface culture. After exposure to either HMGB1 or ATP in vitro, SNECs were processed for messenger RNA (mRNA) extraction and immunocytochemistry. IL-33 levels were determined by real-time polymerase chain reaction (PCR) and by immunochemical staining with anti-IL-33 antibody.
Intranuclear IL-33 is normally expressed in basal epithelial cells, but is present in more apical cells and outside the nucleus in CRSwNP. Exposure of SNECs to HMGB-1 or ATP resulted in a statistically significant increase in IL-33 mRNA expression in SNECs derived from recalcitrant CRSwNP patients. This increase was reflected at the protein level by immunochemical staining of IL-33.
Tissue damage is a nonspecific trigger of epithelial IL-33 production in treatment-recalcitrant polyps, which may be responsible for perpetuating eosinophilic inflammation in CRSwNP. This common pathway may help explain why multiple environmental and infectious agents have been implicated in CRSwNP exacerbation.