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VIP modulates human macrophages phenotype via FPRL1 via activation of RhoA-GTPase and PLC pathways

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Abstract

Objective and design

This study is aimed at uncovering the signaling pathways activated by vasoactive intestinal peptide in human macrophages

Materials

Human peripheral blood mononuclear cell-derived macrophages were used for the in vitro investigation of the VIP-activated signaling pathways.

Methods and treatment

Time-course and dose–response experiments and siRNA were used in human macrophages co-challenged with various concentrations of VIP and different MAPK pharmacologic inhibitors to investigate signaling pathways activated by VIP. Flow analysis was performed to assess the levels of CD11b, CD35 and CD66. Luminescence spectrometry was used to measure the levels of the released hydrogen peroxide and the intracellular calcium levels in the media.

Results

Macrophages incubated with VIP showed increased phospho-AKT and phospho-ERK1/2 levels in a GTP-RhoA-GTPase-dependent manner. Similarly, VIP increased intracellular release of H2O2 and calcium via PLC and GTP-RhoA-GTPase, in addition to inducing the expression of CD11b, CD35, CD66 and MMP9. Furthermore, VIP activated P38 MAPK through the cAMP/PKA pathway but was independent of both PLC and RhoA signaling. The above-mentioned VIP effects were mediated via activation of the FPRL1 receptor.

Conclusion

VIP/FPRL1/VPAC/GTP-RhoA-GTPase signaling modulated macrophages phenotype through activation of multiple signaling pathways including ERK1/2, AKT, P38, ROS, cAMP and calcium.

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Author notes

  1. Zeina Harhous and Wissam H. Faour contributed equally to this work

Authors and Affiliations

  1. Gilbert and Rose-Marie Chagoury School of Medicine, Lebanese American University, P.O. Box 36, Byblos, Lebanon

    Zeina Harhous & Wissam H. Faour

  2. Department of Chemistry and Biochemistry, Faculty of Sciences, Lebanese University, Rafic Hariri University Campus Hadath, Branch 1, Beirut, Lebanon

    Nabil El Zein

Authors
  1. Zeina Harhous
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  2. Wissam H. Faour
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  3. Nabil El Zein
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Correspondence to Nabil El Zein.

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Harhous, Z., Faour, W.H. & El Zein, N. VIP modulates human macrophages phenotype via FPRL1 via activation of RhoA-GTPase and PLC pathways. Inflamm. Res. 70, 309–321 (2021). https://doi.org/10.1007/s00011-021-01436-3

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  • DOI: https://doi.org/10.1007/s00011-021-01436-3

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