Correlation Between HMGB1 and TLR4 Expression in Sinonasal Mucosa in Patients With Chronic Rhinosinusitis

Ear Nose Throat J. 2019 Dec;98(10):599-605. doi: 10.1177/0145561319858915. Epub 2019 Jun 26.


Objectives: Chronic rhinosinusitis (CRS) is one of the most common inflammations in the upper airway. Despite the wide prevalence of CRS, the pathogenesis of this disease is poorly understood. Several components of the innate immune system may play a significant role in CRS, including Toll-like receptor 4 (TLR4), TLR9, and high-mobility group box 1 protein (HMGB1). This study was conducted to determine the expression of TLR4, TLR9, HMGB1, and pNFκ-B p65 in paraffin-embedded blocks of patients with CRS with nasal polyps compared with those of the control group.

Methods: Twenty-six formalin-fixed, paraffin-embedded samples from patients with confirmed CRS and 26 patients undergoing septoplasty due to anatomic variations and no other inflammatory nasal diseases as the control group were assessed. Expression patterns of HMGB1, TLR9, TLR4, and pNFκ-B p65 genes were examined using real-time quantitative reverse transcription polymerase chain reaction (Real-Time qRT-PCR). Statistical analyses were performed with SPSS and analyzed using unpaired 2-tailed t tests or 1-way analysis of variance.

Results: Real-time PCR showed that the expression level of HMGB1 messenger RNA was significantly increased in the tissues of patients with CRS compared with controls (P < .05). The other 3 genes were also upregulated in the patients, but were not significant compared with control. Analysis of the Pearson correlation coefficient (r) revealed a significant positive correlation between HMGB1 and TLR4 (r = 0.79, P < .05) in patients and negative correlation between TLR4 and NfκB in the control group (r = 0.94; P < .05).

Conclusions: Both HMGB1 and TLR4 are increased in the paranasal sinus mucosa of patients with CRS. These results suggest a possible contribution of HMGB1 and its internal receptor (TLR4) in the pathophysiology of CRS.

Keywords: HMGB1; TLR4; inflammation; rhinosinusitis.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biopsy
  • Case-Control Studies
  • Child
  • Chronic Disease
  • Female
  • HMGB1 Protein / metabolism*
  • Humans
  • Male
  • Middle Aged
  • Nasal Mucosa / metabolism
  • Nasal Mucosa / pathology
  • Nasal Polyps / genetics*
  • Nasal Polyps / pathology
  • Paranasal Sinuses / metabolism
  • Paranasal Sinuses / pathology
  • RNA, Messenger / metabolism
  • Rhinitis / genetics*
  • Rhinitis / pathology
  • Sinusitis / genetics*
  • Sinusitis / pathology
  • Toll-Like Receptor 4 / metabolism*
  • Young Adult


  • HMGB1 Protein
  • HMGB1 protein, human
  • RNA, Messenger
  • TLR4 protein, human
  • Toll-Like Receptor 4