The Role of in Regulating Airway Immune Dysfunction in COPD Through the Transforming Growth Factor-Beta/Polymeric Immunoglobulin Receptor Pathway: An In Vitro Study.

BACKGROUND

Chronic obstructive pulmonary disease (COPD) is characterized by progressive airway inflammation and compromised immune defense, often worsened by reduced secretory immunoglobulin A (sIgA) levels. This decline in sIgA is linked to diminished polymeric immunoglobulin receptor (pIgR) activity, which impairs mucosal immunity. MicroRNA-144 (miR-144), a microRNA implicated in inflammation, may contribute to pIgR suppression, though this pathway in COPD remains poorly understood.

METHODS

Human bronchial epithelial cells were exposed to cigarette smoke extract (CSE) to mimic COPD conditions, and were subsequently divided into control and CSE-treated groups. miR-144 was either inhibited or overexpressed in these cells via transient transfection. Expression levels of miR-144, transforming growth factor beta-induced factor homeobox 1 (TGIF-1), transforming growth factor beta (TGF-β), and pIgR were analyzed using quantitative real-time polymerase chain reaction and Western blot. Additionally, a TGF-β inhibitor was applied to assess TGF-β's role in miR-144-mediated regulation of pIgR.

RESULTS

CSE treatment significantly upregulated miR-144 and TGIF-1 while reducing TGF-β and pIgR expression. miR-144 inhibition restored TGF-β and pIgR levels, while miR-144 overexpression reduced them further, indicating miR-144's direct influence on this regulatory pathway. TGF-β inhibition enhanced the reduction of pIgR under miR-144 overexpression, underscoring TGF-β's key role in pIgR regulation.

CONCLUSION

miR-144 mediates immune suppression in COPD by downregulating pIgR through the TGF-β pathway, suggesting that miR-144 could serve as a therapeutic target to restore airway immune function and mitigate disease progression in COPD.