Background: Nuclear factor κB (NF-κB) is a vital transcription factor that is activated by numerous inflammatory stimuli. Its activity is tightly regulated by a family of deubiquitinating enzymes (A20, Cezanne, cylindromatosis [CYLD]) that function in a negative-feedback loop, a process that prevents chronic and systemic inflammation. This study seeks to characterize the expression and functional role of NF-κB-regulating deubiquitinases in the sinonasal epithelium.
Methods: Expression of A20, Cezanne, and CYLD was assessed in normal sinonasal tissue using immunohistochemistry. Cultured sinonasal epithelial cells (SNECs) were stimulated with proinflammatory cytokines (tumor necrosis factor α [TNF-α], interleukin 4 [IL]-4, IL-13) or lipopolysaccharide (LPS) and changes in NF-κB activation and deubiquitinase expression were assessed using Western blots and quantitative real-time polymerase chain reaction (qRT-PCR), respectively.
Results: NF-κB was activated in response to LPS and TNF-α, but not IL-4 or IL-13. A20, Cezanne, and CYLD were all expressed in sinonasal tissue, primarily along the apical surface of the epithelium. Proinflammatory mediators primarily affected expression of A20, with upregulation by LPS and TNF-α and downregulation by IL-4 and IL-13.
Conclusion: The NF-κB-regulating deubiquitinases A20, Cezanne, and CYLD are expressed in sinonasal tissue and are differentially induced by proinflammatory cytokines and the microbial antigen, LPS. These results suggest an important role for NF-κB-regulating deubiquitinases in mucosal immunity and homeostasis.
Keywords: A20; CYLD; Cezanne; NF-κB; TNFAIP3; deubiquitinase; epithelial cell; inflammation; rhinosinusitis; sinonasal.
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