ALI data

Vasoactive intestinal peptide (VIP) is one of the neurotransmitters released by nonadrenergic noncholinergic inhibitory nerve endings. In lung tissues, VIP can inhibit alveolar macrophage phagocytosis and T lymphocyte proliferation, reduce the release of inflammatory mediators, and promote the repair of airway epithelial damage, thus playing an important role in treating pulmonary systemic diseases. This study aimed to explore the effects of VIP on lipopolysaccharide (LPS)-induced macrophage activation in vitro and LPS-induced acute lung injury (ALI) in mice. Mouse primary alveolar macrophage cells were treated with LPS (100 ng/mL) for 8 h and then co-incubated with different concentrations of VIP (108–106 mol/L) for 24 h. VIP treatment significantly inhibited LPS-induced alveolar macrophage M1 polarization and decreased the activation of the nuclear transcription factor-κB (NF-κB) signaling pathway. Subsequent studies confirmed that VIP-inhibited alveolar macrophage M1 polarization and NF-κB signaling pathway activation were dependent on the activation of Adenosine cyclic 3', 5'-monophosphate(cAMP)-protein kinase A(PKA)pathway. ALI was induced in mice by intraperitoneal (ip) injection of LPS (10 mg/kg), and different doses of VIP (1, 3, and 5 nmol/mouse, ip) were administered at 0, 8, and 16 h after LPS injection. VIP significantly reduced LPS-induced inflammatory cell infiltration, decreased the production of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6), and eliminated LPS-mediated pulmonary edema. Also, LPS-induced alveolar macrophage M1 polarization and NF-κB signaling pathway activation were inhibited. In conclusion, VIP could effectively reduce the LPS-induced inflammatory responses in vitro and in vivo; this beneficial effect was associated with the activation of cAMP-PKA pathway and the inhibition of NF-κB signaling pathway activation, thereby reducing the expression of pro-inflammatory mediators and cytokines. These data suggest that VIP may be a potential drug for the treatment of ALI.