PACAP and VIP Modulate LPS-Induced Microglial Activation and Trigger Distinct Phenotypic Changes in Murine BV2 Microglial Cells
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...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-10-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/22/20/10947 |
| _version_ | 1797514383351349248 |
|---|---|
| author | Jocelyn Karunia Aram Niaz Mawj Mandwie Sarah Thomas Broome Kevin A. Keay James A. Waschek Ghaith Al-Badri Alessandro Castorina |
| author_facet | Jocelyn Karunia Aram Niaz Mawj Mandwie Sarah Thomas Broome Kevin A. Keay James A. Waschek Ghaith Al-Badri Alessandro Castorina |
| author_sort | Jocelyn Karunia |
| collection | DOAJ |
| description | 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 <i>Iba1</i> and <i>iNOS</i> (### <i>p</i> < 0.001), as well as the pro-inflammatory mediators <i>IL-1β</i>, <i>IL-6</i>, <i>Itgam</i> and <i>CD68</i> (### <i>p</i> < 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 somata (48.41% vs. 31.36% in LPS-treated cells). 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. |
| first_indexed | 2024-03-10T06:30:51Z |
| format | Article |
| id | doaj.art-7e7ecb064d294544bf917f9633491e98 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T06:30:51Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-7e7ecb064d294544bf917f9633491e982023-11-22T18:31:13ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-10-0122201094710.3390/ijms222010947PACAP and VIP Modulate LPS-Induced Microglial Activation and Trigger Distinct Phenotypic Changes in Murine BV2 Microglial CellsJocelyn Karunia0Aram Niaz1Mawj Mandwie2Sarah Thomas Broome3Kevin A. Keay4James A. Waschek5Ghaith Al-Badri6Alessandro Castorina7Laboratory of Cellular and Molecular Neuroscience (LCMN), School of Life Sciences, Faculty of Science, University of Technology Sydney, Sydney, NSW 2007, AustraliaLaboratory of Cellular and Molecular Neuroscience (LCMN), School of Life Sciences, Faculty of Science, University of Technology Sydney, Sydney, NSW 2007, AustraliaLaboratory of Cellular and Molecular Neuroscience (LCMN), School of Life Sciences, Faculty of Science, University of Technology Sydney, Sydney, NSW 2007, AustraliaLaboratory of Cellular and Molecular Neuroscience (LCMN), School of Life Sciences, Faculty of Science, University of Technology Sydney, Sydney, NSW 2007, AustraliaSchool of Medical Science, [Neuroscience] and Brain and Mind Centre, The University of Sydney, Sydney, NSW 2006, AustraliaIntellectual Development and Disabilities Research Centre, Semel Institute for Neuroscience and Human Behaviour/Neuropsychiatric Institute, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA 90095, USALaboratory of Cellular and Molecular Neuroscience (LCMN), School of Life Sciences, Faculty of Science, University of Technology Sydney, Sydney, NSW 2007, AustraliaLaboratory of Cellular and Molecular Neuroscience (LCMN), School of Life Sciences, Faculty of Science, University of Technology Sydney, Sydney, NSW 2007, AustraliaPituitary 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 <i>Iba1</i> and <i>iNOS</i> (### <i>p</i> < 0.001), as well as the pro-inflammatory mediators <i>IL-1β</i>, <i>IL-6</i>, <i>Itgam</i> and <i>CD68</i> (### <i>p</i> < 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 somata (48.41% vs. 31.36% in LPS-treated cells). 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.https://www.mdpi.com/1422-0067/22/20/10947microglial activationPACAPVIPmorphological analysesBV2inflammatory markers |
| spellingShingle | Jocelyn Karunia Aram Niaz Mawj Mandwie Sarah Thomas Broome Kevin A. Keay James A. Waschek Ghaith Al-Badri Alessandro Castorina PACAP and VIP Modulate LPS-Induced Microglial Activation and Trigger Distinct Phenotypic Changes in Murine BV2 Microglial Cells International Journal of Molecular Sciences microglial activation PACAP VIP morphological analyses BV2 inflammatory markers |
| title | PACAP and VIP Modulate LPS-Induced Microglial Activation and Trigger Distinct Phenotypic Changes in Murine BV2 Microglial Cells |
| title_full | PACAP and VIP Modulate LPS-Induced Microglial Activation and Trigger Distinct Phenotypic Changes in Murine BV2 Microglial Cells |
| title_fullStr | PACAP and VIP Modulate LPS-Induced Microglial Activation and Trigger Distinct Phenotypic Changes in Murine BV2 Microglial Cells |
| title_full_unstemmed | PACAP and VIP Modulate LPS-Induced Microglial Activation and Trigger Distinct Phenotypic Changes in Murine BV2 Microglial Cells |
| title_short | PACAP and VIP Modulate LPS-Induced Microglial Activation and Trigger Distinct Phenotypic Changes in Murine BV2 Microglial Cells |
| title_sort | pacap and vip modulate lps induced microglial activation and trigger distinct phenotypic changes in murine bv2 microglial cells |
| topic | microglial activation PACAP VIP morphological analyses BV2 inflammatory markers |
| url | https://www.mdpi.com/1422-0067/22/20/10947 |
| work_keys_str_mv | AT jocelynkarunia pacapandvipmodulatelpsinducedmicroglialactivationandtriggerdistinctphenotypicchangesinmurinebv2microglialcells AT aramniaz pacapandvipmodulatelpsinducedmicroglialactivationandtriggerdistinctphenotypicchangesinmurinebv2microglialcells AT mawjmandwie pacapandvipmodulatelpsinducedmicroglialactivationandtriggerdistinctphenotypicchangesinmurinebv2microglialcells AT sarahthomasbroome pacapandvipmodulatelpsinducedmicroglialactivationandtriggerdistinctphenotypicchangesinmurinebv2microglialcells AT kevinakeay pacapandvipmodulatelpsinducedmicroglialactivationandtriggerdistinctphenotypicchangesinmurinebv2microglialcells AT jamesawaschek pacapandvipmodulatelpsinducedmicroglialactivationandtriggerdistinctphenotypicchangesinmurinebv2microglialcells AT ghaithalbadri pacapandvipmodulatelpsinducedmicroglialactivationandtriggerdistinctphenotypicchangesinmurinebv2microglialcells AT alessandrocastorina pacapandvipmodulatelpsinducedmicroglialactivationandtriggerdistinctphenotypicchangesinmurinebv2microglialcells |