Mannose prevents acute lung injury through mannose receptor pathway and contributes to regulate PPARγ and TGF-ß1 level.

ABSTRACT

Mannose has been reported to prevent acute lung injury (ALI), and mannose receptor (MR) has been demonstrated to have a role. The rationale for this study is to characterize the mechanism by which mannose and MR prevent lipopolysaccharide (LPS)-induced ALI. Male ICR mice were pretreated mannose by intravenous injection 5 min before and 3 h after intratracheal instillation of LPS. Pathological changes, proinflammatory mediator, peroxisome proliferator activated receptor gamma (PPARγ), MR, and transforming growth factor ß1 (TGF-ß1) levels were determined. The RAW264.7 cells were pretreated with mannose and stimulated with LPS for 3 h. Proinflammatory mediator and TGF-ß1 in the culture media, PPARγ, MR, and TGF-ß1 expression in RAW 264.7 cells were measured. Mannose markedly attenuated the LPS-induced histological alterations and inhibited the production of proinflammatory mediator in mice and in RAW 264.7 cells. Mannose increased PPARγ and MR expression, and inhibited TGF-ß1 stimulated by LPS. Interestingly, competitive inhibition of MR with mannan was associated with elimination of the anti-inflammatory effects of mannose, and reversed effects of mannose of regulation to PPARγ and TGF-ß1. MR is important in increasing PPARγ and decreasing TGF-ß1 expression and plays a critical role in mannose's protection against ALI.