DMBT1 has a protective effect on allergic rhinitis

Biomed Pharmacother. 2020 Jan;121:109675. doi: 10.1016/j.biopha.2019.109675. Epub 2019 Nov 25.

Abstract

Objective: Deleted in malignant brain tumors 1 (DMBT1) is a secreted scavenger receptor cysteine-rich (SRCR) protein, predominantly expressed in nasal mucosal epithelial cells. In previous experiments, we found large amounts of DMBT1 present in the nasal cavity mucosa of allergic rhinitis (AR) patients. However, the exact role of DMBT1 in AR remains unclear. This study is to investigate the mechanism through which DMBT1 exerts its effects on AR progression.

Method: DMBT1 levels in the nasal lavage (NL) fluid and the nasal mucosa in AR and control groups were determined by ELISA and IHC. Next, mice were sensitized with ovalbumin; intranasal administrations of recombinant DMBT1 were then performed. DMBT1 in the nasal mucosa of mice were determined by IHC and WB. Nasal symptoms were estimated. IL-4 and IL-5 in BAL fluid and eosinophils infiltration in the nasal cavity were measured through ELISA and HE staining, respectively.

Results: DMBT1 levels were found to be significantly higher in the NL fluid and nasal mucosa of AR patients and AR mice, compared to control groups (p < 0.01). Levels of IL-4 and IL-5 in BAL and infiltration of eosinophils into the nasal mucosa were significantly increased in AR mice, compared to control mice (p < 0.01). rDMBT1 significantly reduced the number of nasal sneezing and rubbings in AR mice (p < 0.01). It also inhibited the eosinophil infiltration in the nasal mucosa and significantly decreased the production of IL-4 and IL-5 in BAL (p < 0.01).

Conclusion: This study demonstrated that rDMBT1 alleviates AR progression in mice via inhibiting IL-4 and IL-5 production and eosinophils infiltration in the nasal cavity.

Keywords: Allergic rhinitis (AR); DMBT1; Interleukin-4 (IL-4); Interleukin-5 (IL-5).

MeSH terms

  • Administration, Intranasal
  • Animals
  • Bronchoalveolar Lavage Fluid
  • Calcium-Binding Proteins / metabolism*
  • DNA-Binding Proteins / metabolism*
  • Disease Models, Animal
  • Disease Progression
  • Eosinophils / metabolism
  • Humans
  • Immunoglobulin E / blood
  • Interleukin-4 / metabolism
  • Interleukin-5 / metabolism
  • Linear Models
  • Male
  • Mice, Inbred BALB C
  • Nasal Lavage Fluid
  • Nasal Mucosa / metabolism
  • Nasal Mucosa / pathology
  • Protective Agents / metabolism*
  • Recombinant Proteins / pharmacology
  • Rhinitis, Allergic / blood
  • Rhinitis, Allergic / metabolism*
  • Rhinitis, Allergic / pathology
  • Rhinitis, Allergic / physiopathology
  • Sneezing / drug effects
  • Tumor Suppressor Proteins / metabolism*

Substances

  • Calcium-Binding Proteins
  • DMBT1 protein, human
  • DNA-Binding Proteins
  • Dmbt1 protein, mouse
  • Interleukin-5
  • Protective Agents
  • Recombinant Proteins
  • Tumor Suppressor Proteins
  • Interleukin-4
  • Immunoglobulin E