Effects of Vasoactive Intestinal Peptide on M1/M2 Polarization and Related Cytokines in Alveolar Macrophages

OBJECTIVE To observe the effects of vasoactive intestinal peptide(VIP) on M1/M2 polarization and related cytokines of alveolar macrophages(AM). METHODS Lipopolysaccharide(LPS) combined with interferon-γ(IFN-γ) and interleukin-4(IL-4) combined with interleukin-13(IL-13) were used to induce M1/M2 type polarization of AM, and then VIP (10^-8-10^-6 mol·L^-1) was used to intervene the polarization of AM. The co-expression of M1 type AM marker CD86 and pro-inflammatory factor interleukin 6(IL-6) and co-expression of M2-type AM marker CD206 and anti-inflammatory factor interleukin 10(IL-10) was determined by immunofluorescence double standard method. Expression of IL-6, tumor necrosis factor-α(TNF-α), IL-10 and arginase-1(Arg-1) in cell supernatant was detected by ELISA. The macrophage surface markers CD86, CD206 and macrophage related factors IL-6, TNF-α, inducible nitric oxide synthase(iNOS), IL-10, Arg-1 and chitinase 3-like 3(Ym1) were detected by RT-PCR. RESULTS After induction by LPS combined with IFN-γ and IL-4 combined with IL-13, AM was polarized to M1/M2 type respectively. The activation and release of pro-inflammatory factors IL-6, TNF-α and iNOS related to M1 and anti-inflammatory factors IL-10, Arg-1 and Ym1 related to M2 were significantly higher than those in the uninduced normal group(P<0.05). Interference with different concentrations of VIP(10^-8-10^-6 mol·L^-1) could down-regulate the activity and expression of M1 type AM and related inflammatory cytokines IL-6, TNF-α and iNOS(P<0.05). The activity and expression of M2 type AM and related anti-inflammatory factors IL-10, Arg-1 and Ym1 were up-regulated(P<0.05). CONCLUSION VIP can inhibit AM M1-type polarization and reduce the activation and release of inflammatory cytokines IL-6, TNF-α and iNOS. It can promote AM M2-type polarization and increase the activation and release of anti-inflammatory factors IL-10, Arg-1 and Ym1, suggesting that VIP may inhibit the inflammatory response and play a protective role in lung tissue by regulating the M1/M2-type polarization of AM in the process of pulmonary inflammation.