Different intensity of autophagy regulate interleukin-33 to control the uncontrolled inflammation of acute lung injury

Cytokines participate in the progression of acute respiratory distress syndrome (ARDS), and uncontrolled inflammation is a central issue of acute lung injury (ALI). Interleukin (IL)-33 is a nuclear protein that has been reported to have a proinflammatory role in ARDS. Studies have shown that excessive autophagy may lead to the increased mortality of patients with ARDS, while several investigations indicated that IL-33 and autophagy interact with one another. The present study sought to clarify the relation between autophagy and IL-33’s proinflammatory role in ARDS.

We built a lipopolysaccharide (LPS)-induced lung injury mouse model. To study the relationship between IL-33 and autophagy, mice were pretreated with rapamycin (RAPA; a promoter of autophagy) and 3-methyladenine (3-MA; an inhibitor of autophagy) prior to LPS administration. The expression of IL-33 in serum and bronchoalveolar lavage fluid (BALF) was measured. Immunohistochemistry of IL-33 in lung tissue was examined. Th1,Th2 cytokines/chemokine levels in serum and BALF were tested. Further, the severity of lung injury was evaluated. And the nuclear factor-kappa B (NF-κB)'s nuclear translocation in lung tissue was detected.

In comparison with the control group, the levels of IL-33 in serum and BALF were increased after LPS injection. Th1 cytokines/chemokine levels were significantly increased in serum and BALF, while Th2 cytokine levels changed only a little. The levels of IL-33 in serum and BALF of the RAPA group was significantly increased after LPS was injected as compared with the LPS group; additionally, the levels of IL-33 in serum and BALF of the 3-MA group was significantly reduced after LPS was injected as compared with the LPS group, and that lung injury was ameliorated after 3-MA pretreatment. Th1 cytokines and chemokines in both serum and BALF were also decreased in the 3-MA group. Furthermore, we found that the nuclear translocation of NF-κB increased after LPS administration, and NF-κB’s nuclear translocation was significantly increased in comparison with the LPS group after RAPA pretreatment. In contrast, NF-κB’s nuclear translocation decreased after 3-MA pretreatment as compared with the LPS group.

These findings showed that autophagy might regulate IL-33 by activating or inhibiting NF-κB to control the uncontrolled inflammation of acute lung injury.