Pediatric
asthma is a chronic pulmonary inflammatory disease featuring hypersecretion of mucus and
inflammation in the airway, resulting in dysfunction of the airway smooth muscle. Previous evidence demonstrated that latrophilins, a novel family of receptors, present a beneficial effect on airway smooth muscle cells. In the present study, the
therapeutic effects of recombinant human
latrophilin 3 (rhLPHN3) antibody (Ab) in patients with pediatric
asthma were investigated, and the molecular mechanism underlying the function of LPHN3 in the treatment of
asthma in clinical practice was examined. A total of 342 pediatric
asthma cases were recruited and randomly divided into three groups, receiving treatment with rhLPHN3 Ab (n=134),
salbutamol (n=108) or
montelukast (n=100) by nasal aerosolization. Each group received the respective clinically tested dose for 16 weeks. Inflammatory factors
interleukin (IL)-10,
IL-17,
IL-4, matrix metallopeptidase-9 (MMP-9),
interferon-γ (IFN-γ) and
transforming growth factor-β (TGF-β) levels in peripheral blood mononuclear cells were analyzed prior to and post treatment. The clinical outcomes revealed that pathological alterations were significantly improved following treatment with rhLPHN3 Ab for patients with pediatric
asthma when compared with those receiving
salbutamol and
montelukast. It was also observed that rhLPHN3 Ab downregulated the plasma concentration levels of
IL-10,
IL-17,
IL-4 and MMP-9, and upregulated IFN-γ and TGF-β levels in the three groups. In addition, clinical data demonstrated that rhLPHN3 Ab significantly promoted
E-selectin and
mucin 5AC expression, as well as improved the activation of nuclear factor (NF)-κB p65
DNA binding activity and the phosphorylation levels of
protein kinase A. Furthermore, rhLPHN3 Ab markedly improved adhesion and proliferation of airway smooth muscle cells, which led to promotion of the contraction of these cells. In conclusion, these clinical data suggest that rhLPHN3 Ab serves an important role in the inhibition of inflammatory mediators through downregulation of NF-κB signaling pathway, which contributes to
airway remodeling and bronchodilation in patients with pediatric
asthma.