The deleted in malignant brain tumors 1 (DMBT1) protein participates in cystic fibrosis (CF)-associated inflammatory processes and may have diagnostic and therapeutic value, according to a new study published in Molecular and Cellular Pediatrics.

The authors found increased expression of DMBT1 in formalin-fixed, paraffin-embedded lung sections from patients with CF compared to control specimens (without lung disease). Accordingly, the pulmonary expression of Dmbt1 was nearly 6-fold higher in a transgenic mouse model of CF-like lung disease than in wild-type mice.

DMBT1-positive mucus and DMBT1-positive macrophages were observed in the alveoli and small airways of the patients with CF. The addition of human recombinant DMBT1 to human respiratory epithelial cells had a negative effect on ciliary motility and led to irregular beat waves.

“This finding suggests that increased DMBT1 levels in patients with CF may impede the ciliary function and thus mucus removal,” the authors said.

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Treatment of lung carcinoma epithelial cells with acetylcysteine, which is known to inhibit the synthesis of mucins and proinflammatory mediators after viral infections, reduced the concentration of DMBT1 in the cell culture medium.

The potential role of acetylcysteine in CF treatment remains controversial. Besides regulating DMBT1, it has been shown to reduce several inflammatory markers’ levels and has antibacterial properties. However, the few meta-analyses and clinical studies available addressing the therapeutic effect of acetylcysteine in patients with CF did not show a clear added value.

Nonetheless, Kiefer et al said that “a positive effect of [acetylcysteine] therapy (inhaled or oral) on clinical outcome/on airway inflammation cannot be ruled out, as studies that use more sensitive parameters such as multiple breath washout or [magnetic resonance imaging] imaging are lacking in the literature.”

Reference

Kiefer A, Plattner E, Ruppel R, et al. DMBT1 is upregulated in cystic fibrosis, affects ciliary motility, and is reduced by acetylcysteine. Mol Cell Pediatr. 2022;9(1):4. doi:10.1186/s40348-022-00136-0