Insulin‑like growth factor 1 inhibits phagocytosis of alveolar epithelial cells in asthmatic mice

Abstract

The phagocytosis of apoptotic cells by alveolar epithelial cells helps to eliminate airway inflammation. Insulin‑like growth factor 1 (IGF‑1) regulates cell metabolism and proliferation, and promotes cell survival, while it may also promote the proliferation and differentiation of alveolar epithelial cells during the repair of lung injury. The present study investigated the effect of IGF‑1 on the phagocytic activity of alveolar epithelial cells, a nonprofessional phagocyte. IGF‑1 was elevated in lung tissue and bronchoalveolar lavage fluid obtained from mice with ovalbumin‑induced asthma. IGF‑1 was reduced by 50% in the lung tissue and by nearly 100% in the bronchoalveolar lavage fluid in asthmatic mice established by depletion of alveolar macrophages using 2‑chloroadenosine. In addition, interleukin‑33 induced IGF‑1 production in primary alveolar macrophages. It was also observed that IGF‑1 inhibited the phagocytosis of fluorescent microspheres and apoptotic cells by MLE‑12 alveolar epithelial cells. Antibody blocking of IGF‑1 enhanced the phagocytosis of fluorescent microspheres and apoptotic cells, and significantly reduced inflammatory cell infiltration in airway and perivascular tissues. The elevated IGF‑1 level in the lungs of asthma model mice was mainly produced in alveolar macrophages. Taken together, the current study demonstrated that IGF‑1 inhibited phagocytosis by alveolar epithelial cells, and that IGF‑1 blockade enhanced the phagocytic activity and alleviated airway inflammation. These results support the potential use of IGF‑1 as a target in the treatment of asthma.