Tumor necrosis factor-α regulates interleukin-33 expression through extracellular signal-regulated kinase, p38, and nuclear factor–κB pathways in airway epithelial cells

Il Ho Park, Joo Hoo Park, Jae Min Shin, Heung Man Lee

Research output: Contribution to journalArticle

8 Citations (Scopus)


Background: Interleukin (IL)-33 plays an important role in controlling immune responses in barrier tissues, and is a potent mediator of inflammatory diseases such as asthma, rheumatoid disease, and chronic rhinosinusitis. The aims of the present study were 2-fold: (1) to determine the stimulatory effect of tumor necrosis factor-α (TNF-α) on IL-33 production in nasal epithelial and A549 cells; and (2) to identify downstream pathways that activate IL-33 production. Methods: Primary nasal epithelial cells (PNECs) from 5 normal patients were isolated and cultured. To identify which cytokines stimulate IL-33 production, we performed reverse-transcription polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and immunofluorescence staining. Three mitogen-activated protein kinases (MAPKs) (p38, extracellular signal-regulated kinase [ERK], and c-Jun N-terminal kinase [JNK]) and nuclear factor κB (NF-κB) were evaluated as downstream signaling molecules by RT-PCR, ELISA, Western blot analysis, and luciferase reporter assay. Results: The IL-33 messenger RNA (mRNA) and protein levels were increased significantly by TNF-α in PNECs and A549 cells. TNF-α stimulated the expression of IL-33 in a dose- and time-dependent manner in A549 cells. PNECs and A549 cells were treated with TNF-α in the presence of specific inhibitors of p38, ERK, JNK, and NF-κB. In both cell types, inhibitors of ERK, p38, and NF-κB reversed TNF-α–induced IL-33 production. In the luciferase reporter assay, NF-κB activity was inhibited not only by an NF-κB inhibitor, but also by ERK and p38 inhibitors. Conclusion: TNF-α stimulated IL-33 expression through ERK, p38, and NFκB pathways in PNECs and A549 cells.

Original languageEnglish
Pages (from-to)973-980
Number of pages8
JournalInternational Forum of Allergy and Rhinology
Issue number9
Publication statusPublished - 2016 Sep 1



  • chronic rhinosinusitis
  • epithelium
  • interleukin-33
  • nose
  • tumor necrosis factor-alpha

ASJC Scopus subject areas

  • Immunology and Allergy
  • Otorhinolaryngology

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