CD26 and Asthma: a Comprehensive Review

Abstract

Asthma is a heterogeneous and chronic inflammatory family of disorders of the airways with increasing prevalence that results in recurrent and reversible bronchial obstruction and expiratory airflow limitation. These diseases arise from the interaction between environmental and genetic factors, which collaborate to cause increased susceptibility and severity. Many asthma susceptibility genes are linked to the immune system or encode enzymes like metalloproteases (e.g., ADAM-33) or serine proteases. The S9 family of serine proteases (prolyl oligopeptidases) is capable to process peptide bonds adjacent to proline, a kind of cleavage-resistant peptide bonds present in many growth factors, chemokines or cytokines that are important for asthma. Curiously, two serine proteases within the S9 family encoded by genes located on chromosome 2 appear to have a role in asthma: CD26/dipeptidyl peptidase 4 (DPP4) and DPP10. The aim of this review is to summarize the current knowledge about CD26 and to provide a structured overview of the numerous functions and implications that this versatile enzyme could have in this disease, especially after the detection of some secondary effects (e.g., viral nasopharyngitis) in type II diabetes mellitus patients (a subset with a certain risk of developing obesity-related asthma) upon CD26 inhibitory therapy.

Glucagon-like peptide 1: A potential anti-inflammatory pathway in obesity-related asthma

“…A pro-inflammatory upregulation can be seen after allergen exposure within the lung (Nieto-Fontarigo et al, 2016). Bronchial epithelial cells from untreated human asthmatics express high levels of DPP-4 that are further enhanced by IL-13, correlating with elevated exhaled nitric oxide levels and proliferation of lung fibroblasts and bronchial smooth muscle (Shiobara et al, 2016).…”

“…DPP-4 appears to activate pro-inflammatory pathways (MAPK and NF-κB) and may also increase generation of reactive oxygen species, AGEs, and RAGE gene expression (Ishibashi et al, 2013; Wronkowitz et al, 2014). Although upregulated DPP-4 may act to downregulate GLP-1’s benefits, the evidence for the use of DPP-4 inhibition in asthma is conflicting (Nader, 2015; Nieto-Fontarigo et al, 2016). …”

The emerging role of dipeptidyl-peptidase-4 as a therapeutic target in lung disease

“…Those enzymes with preferential catalytic activity for proline residues are rare given that peptide bonds that are juxtaposed to proline are extremely resistant to cleavage [28]. These peptide sequences can be found in growth factors and cytokines that play a crucial role in immune dysfunction [29]. Many studies have been conducted to determine any genetic factors which underlie the development of asthma.…”

Diabetes and Lung Disease: A Neglected Relationship

“…Mediated allergic airway inflammation [134]. Sulfonylurea and sulfonylurea-like drugs Glibenclamide has a protective role in asthma development [129].…”