Monomeric IgA promotes cytokine production, proliferation and migration by human airway smooth muscle cells

Abstract

Immunoglobulin A (IgA) is important in biological defense mainly in the mucosal area and has pathogenic and inflammatory roles in various diseases. IgA activates not only inflammatory but also structural cells including airway epithelial cells and fibroblasts. The current study aimed to validate the effect of IgA on bronchial smooth muscle cells (BSMCs), which are another type of cell involved in airway remodeling and responsiveness. Results showed that monomeric IgA (mIgA) induced interleukin (IL)-6, IL-8, and monocyte chemoattractant protein (MCP)-1 production, and enhanced cell proliferation, collagen gel contraction, and BSMC migration. Among previously reported receptors for mIgA, BSMCs expressed TfR/CD71. Transfection with small interference RNA (siRNA) against TfR/CD71 partially inhibited cytokine and chemokine production promoted by mIgA-stimulated BSMCs. Moreover, the mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K)/Akt, and nuclear factor-κB (NF-κB) pathways were activated via mIgA stimulation in BSMCs. Thus, mIgA may activate BSMCs and exacerbate inflammatory lung diseases including asthma.