Regulatory effect of hypoxia-inducible factor-1α on acute lung inflammation

Objective To study the role of hypoxia-inducible factor-1α (HIF-1α) in regulating the acute inflammation of lung. Methods Hif-1α knockout (Hif-1α+ /-) mice and their wild-type (Hif-1α+ /+ ) were stimulated with lipopolysaccharide to establish acute lung injury (ALI) model, respectively.The bronohoalveolar lavage fluid (BALF), blood and lung tissue were collected at 6th, 12th, 24th and 48th hour after LPS treatment.The number of total leukocytes and neutrophils in BALF of ALI model group and control group were counted.The levels of inflammatory factors such as tumor necrosis factor-α and KC in the serum of each group were detected by enzyme linked immunosorbent assay.The neutrophil infiltration in airway and lung tissue of all groups was assessed by hematoxylin-eosin staining.And the neutrophil apoptosis in lung tissue of all groups was detected by TUNEL. Results The number of leukocytes and neutrophils in BALF of Hif-1α+ /- and Hif-1α+ /+ ALI mice was significantly higher than that of control mice.And there was no significant difference in the number of leukocytes in BALF between Hif-1α+ /- and Hif-1α+ /+ ALI mice.But compared to Hif-1α+ /+ ALI mice, the number of neutrophils in BALF of Hif-1α+ /- ALI mice was significantly lower (P<0.05). The levels of TNF-α and KC in serum of both ALI model mice were significantly higher than those in control group.But the levels of TNF-α and KC in the Hif-1α+ /- ALI mice were significantly lower than those in the Hif-1α+ /+ ALI mice.Hematoxylin-eosin staining indicated that there were a large amount of neutrophils infiltrating into the lung tissue and airway of Hif-1α+ /- ALI mice, which were much more than those of Hif-1α+ /+ ALI mice.TUNEL staining further revealed that there were a large number of apoptotic neutrophils in the lung tissue of Hif-1α+ /- ALI mice, which were significantly more than those of Hif-1α+ /+ ALI mice. Conclusions HIF-1α enhances acute lung inflammation by inhibiting neutrophil apoptosis. Key words: Acute inflammation; Neutrophil; Apoptosis; Hypoxia-inducible factor-1, alpha subunit