DISTINCT PHENOTYPIC CHANGES BY PACAP AND VIP IN LIPOPOLYSACCHARIDE STIMULATED BV2 MICROGLIAL CELLS

Karunia, J; Niaz, A; Mandwie, M; Al-Badri, G; Castorina, A

DISTINCT PHENOTYPIC CHANGES BY PACAP AND VIP IN LIPOPOLYSACCHARIDE STIMULATED BV2 MICROGLIAL CELLS

Karunia, J Niaz, A Mandwie, M Al-Badri, G

Castorina, A

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Publication Type:: Conference Proceeding
Citation:: 2019
Issue Date:: 2019-12-01

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Field	Value	Language
dc.contributor.author	Karunia, J	en_US
dc.contributor.author	Niaz, A	en_US
dc.contributor.author	Mandwie, M	en_US
dc.contributor.author	Al-Badri, G https://orcid.org/0000-0003-3342-2376	en_US
dc.contributor.author	Castorina, A https://orcid.org/0000-0001-7037-759X	en_US
dc.date	2019-11-03	en_US
dc.date.available	2019-10-05	en_US
dc.date.issued	2019-12-01	en_US
dc.identifier.citation	2019	en_US
dc.identifier.uri	http://hdl.handle.net/10453/138424
dc.description.abstract	Background: Aberrant microglial activation plays a key role in the progressive neuronal loss seen in many neurodegenerative diseases. PACAP and VIP are two neuropeptides that elicit robust immunosuppressive functions within the CNS. However, the underlying mechanisms through which these peptides regulate microglia activities are not clear. Aim & Objectives: Using lipopolysaccharide (LPS) to induce BV2 microglial cell polarisation, we aimed at testing whether and how administration of either PACAP or VIP could differentially affect microglial pro-inflammatory profile, polarisation state and morphological appearance to elicit immunosuppressive effects. Methods: Quantitative real-time PCR, Western blot, Griess reactions, immunofluorescence and morphological analyses were conducted in order to determine the effects of PACAP and VIP in BV2 microglial cells exposed or not to 1µg/ml LPS. Results: Our data demonstrated that both PACAP and VIP reduce the expression of pro-inflammatory mediators in LPS-stimulated BV2 cells. We also found that exogenous administration of PACAP and VIP rescued the dysregulations of the endogenous PACAP/VIP levels and attenuated the expression of microglial activation markers caused by LPS. Interestingly, despite the similar anti-inflammatory activities of PACAP and VIP, PACAP mainly reduced the number of M1 polarised cells, whereas VIP acted by increasing the subpopulation of cells exhibiting an ‘intermediate’ phenotype/bipolar-shaped (p<0.001 vs. control), at the expenses of resting/rounded cells. Conclusion: PACAP and VIP both possess immunosuppressive effects in activated BV2 microglial cells, but these effects seem to involve the differential shift of certain cell subpopulations towards distinctive phenotypes.	en_US
dc.relation.ispartof	Akira Arimura Memorial VIP/PACAP and Related Peptides Symposium: 30 years after PACAP Discovery	en_US
dc.title	DISTINCT PHENOTYPIC CHANGES BY PACAP AND VIP IN LIPOPOLYSACCHARIDE STIMULATED BV2 MICROGLIAL CELLS	en_US
dc.type	Conference Proceeding
utslib.location.activity	Los Angeles, California	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/DVC (Teaching and Learning)
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
utslib.copyright.status	open_access
pubs.consider-herdc	true	en_US
pubs.finish-date	2019-11-06	en_US
pubs.publication-status	Accepted	en_US
pubs.start-date	2019-11-03	en_US

Abstract:

Background: Aberrant microglial activation plays a key role in the progressive neuronal loss seen in many neurodegenerative diseases. PACAP and VIP are two neuropeptides that elicit robust immunosuppressive functions within the CNS. However, the underlying mechanisms through which these peptides regulate microglia activities are not clear. Aim & Objectives: Using lipopolysaccharide (LPS) to induce BV2 microglial cell polarisation, we aimed at testing whether and how administration of either PACAP or VIP could differentially affect microglial pro-inflammatory profile, polarisation state and morphological appearance to elicit immunosuppressive effects. Methods: Quantitative real-time PCR, Western blot, Griess reactions, immunofluorescence and morphological analyses were conducted in order to determine the effects of PACAP and VIP in BV2 microglial cells exposed or not to 1µg/ml LPS. Results: Our data demonstrated that both PACAP and VIP reduce the expression of pro-inflammatory mediators in LPS-stimulated BV2 cells. We also found that exogenous administration of PACAP and VIP rescued the dysregulations of the endogenous PACAP/VIP levels and attenuated the expression of microglial activation markers caused by LPS. Interestingly, despite the similar anti-inflammatory activities of PACAP and VIP, PACAP mainly reduced the number of M1 polarised cells, whereas VIP acted by increasing the subpopulation of cells exhibiting an ‘intermediate’ phenotype/bipolar-shaped (p<0.001 vs. control), at the expenses of resting/rounded cells. Conclusion: PACAP and VIP both possess immunosuppressive effects in activated BV2 microglial cells, but these effects seem to involve the differential shift of certain cell subpopulations towards distinctive phenotypes.

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http://hdl.handle.net/10453/138424