Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

PACAP and VIP Modulate LPS-induced Microglial Activation and Trigger Distinct Phenotypic Changes in Murine BV2 Microglial Cells

Jocelyn Karunia
,
Aram Niaz
ORCID logo ,
Mawj Mandwie
ORCID logo ,
Sarah Thomas Broome
ORCID logo ,
Kevin A Keay
,
James A Waschek
,
Ghaith Al-Badri
,
Alessandro Castorina
* ORCID logo
Version 1 : Received: 30 August 2021 / Approved: 31 August 2021 / Online: 31 August 2021 (11:11:34 CEST)

A peer-reviewed article of this Preprint also exists.

Karunia, J.; Niaz, A.; Mandwie, M.; Thomas Broome, S.; Keay, K.A.; Waschek, J.A.; Al-Badri, G.; Castorina, A. PACAP and VIP Modulate LPS-Induced Microglial Activation and Trigger Distinct Phenotypic Changes in Murine BV2 Microglial Cells. Int. J. Mol. Sci. 2021, 22, 10947. Karunia, J.; Niaz, A.; Mandwie, M.; Thomas Broome, S.; Keay, K.A.; Waschek, J.A.; Al-Badri, G.; Castorina, A. PACAP and VIP Modulate LPS-Induced Microglial Activation and Trigger Distinct Phenotypic Changes in Murine BV2 Microglial Cells. Int. J. Mol. Sci. 2021, 22, 10947.

Abstract

Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) are two structurally-related immunosuppressive peptides. However, the underlying mechanisms through which these peptides regulate microglial activity are not fully understood. Using lipopolysaccharide (LPS) to induce an inflammatory challenge, we tested whether PACAP or VIP differentially affected microglial activation, morphology and cell migration. We found that both peptides attenuated LPS-induced expression of the microglial activation markers Iba1 and iNOS (###p<0.001), as well as the pro-inflammatory mediators IL-1β, IL-6, Itgam and CD68 (###p<0.001). In contrast, treatment with PACAP or VIP exerted distinct effects on microglial morphology and migration. PACAP reversed LPS-induced soma enlargement and increased the percentage of small-sized, rounded cells (54.09% vs 12.05% in LPS-treated cells), whereas VIP promoted a phenotypic shift towards cell subpopulations with mid-sized, spindle-shaped soma (48.41% vs 31.36% in LPS-treated). Additionally, PACAP was more efficient than VIP in restoring LPS-induced impairment of cell migration and the expression of urokinase plasminogen activator (uPA) in BV2 cells compared with VIP. These results suggest that whilst both PACAP and VIP exert similar immunosuppressive effects in activated BV2 microglia, each peptide triggers distinctive shifts towards phenotypes of differing morphologies and with differing migration capacities.

Keywords

microglial activation; PACAP; VIP; morphological analyses; BV2; inflammatory markers; GFAP; Iba1

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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