Interleukin-34 induces pulmonary inflammation in a murine model of lipopolysaccharide-induced acute lung injury

Abstract

The cytokine interleukin-34 （IL-34） was recently described. However, its role in the lungs is not well understood. IL-34 binds to the colony stimulating factor-1 receptor, thereby enhancing tissue macrophage maturation and differentiation. Macrophages are essential to the airway inflammation process and acute lung injury （ALI）. This study aimed to evaluate the role of IL-34 in ALI establishment. C57BL/6 male mice were stimulated intratracheally with lipopolysaccharide （LPS） and sacrificed on day 1, 3, 5, or 7. Additionally, the mice were treated with an anti-IL-34 antibody intranasally before LPS stimulation. The bronchoalveolar lavage fluid （BALF） and lung tissues were collected. The cells of the human peripheral blood monocyte cell line THP-1 and the human airway epithelial cell line BEAS-2B were cultured with LPS in vitro. The total cell number in BALF was higher in the LPS-stimulated mice than in the control mice. The BALF IL-34 level was significantly elevated in BALF on days 1 and 3. IL-34 expression was detected in the pulmonary epithelium in the LPS-stimulated mice on day 1. Anti-IL-34 antibody suppressed the number of macrophages in BALF. IL-34 blockade resulted in pulmonary fibrosis reduction in LPS-stimulated mice on day 5. LPS stimulation in vitro induced the production of tumor necrosis factor-α （TNF-α） in THP-1 cells. Furthermore, TNF-α stimulation induced the IL-34 production in BEAS-2B cells. These results suggest that IL-34 induction in the epithelial cells may enhance pulmonary inflammation and fibrosis in the murine model of LPS-induced acute lung injury.