Characterization of Lipopolysaccharide Effects on LRRK2 Signaling in RAW Macrophages
Dysfunction of the immune system and mitochondrial metabolism has been associated with Parkinson’s disease (PD) pathology. Mutations and increased kinase activity of leucine-rich repeat kinase 2 (LRRK2) are linked to both idiopathic and familial PD. However, the function of LRRK2 in the immune cells...
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MDPI AG
2023-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/2/1644 |
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| author | Asmaa Oun Emmy Hoeksema Ahmed Soliman Famke Brouwer Fabiola García-Reyes Henderikus Pots Marina Trombetta-Lima Arjan Kortholt Amalia M. Dolga |
| author_facet | Asmaa Oun Emmy Hoeksema Ahmed Soliman Famke Brouwer Fabiola García-Reyes Henderikus Pots Marina Trombetta-Lima Arjan Kortholt Amalia M. Dolga |
| author_sort | Asmaa Oun |
| collection | DOAJ |
| description | Dysfunction of the immune system and mitochondrial metabolism has been associated with Parkinson’s disease (PD) pathology. Mutations and increased kinase activity of leucine-rich repeat kinase 2 (LRRK2) are linked to both idiopathic and familial PD. However, the function of LRRK2 in the immune cells under inflammatory conditions is contradictory. Our results showed that lipopolysaccharide (LPS) stimulation increased the kinase activity of LRRK2 in parental RAW 264.7 (WT) cells. In addition to this, LRRK2 deletion in LRRK2 KO RAW 264.7 (KO) cells altered cell morphology following LPS stimulation compared to the WT cells, as shown by an increase in the cell impedance as observed by the xCELLigence measurements. LPS stimulation caused an increase in the cellular reactive oxygen species (ROS) levels in both WT and KO cells. However, WT cells displayed a higher ROS level compared to the KO cells. Moreover, <i>LRRK2</i> deletion led to a reduction in interleukin-6 (IL-6) inflammatory cytokine and cyclooxygenase-2 (COX-2) expression and an increase in lactate production after LPS stimulation compared to the WT cells. These data illustrate that LRRK2 has an effect on inflammatory processes in RAW macrophages upon LPS stimulation. |
| first_indexed | 2024-03-09T12:19:07Z |
| format | Article |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T12:19:07Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-b0900ecdabac4994bc8ac991fa5ff09d2023-11-30T22:43:31ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-01-01242164410.3390/ijms24021644Characterization of Lipopolysaccharide Effects on LRRK2 Signaling in RAW MacrophagesAsmaa Oun0Emmy Hoeksema1Ahmed Soliman2Famke Brouwer3Fabiola García-Reyes4Henderikus Pots5Marina Trombetta-Lima6Arjan Kortholt7Amalia M. Dolga8Department of Molecular Pharmacology, Faculty of Science and Engineering, Groningen Research Institute of Pharmacy (GRIP), University of Groningen, 9713 AV Groningen, The NetherlandsDepartment of Molecular Pharmacology, Faculty of Science and Engineering, Groningen Research Institute of Pharmacy (GRIP), University of Groningen, 9713 AV Groningen, The NetherlandsDepartment of Molecular Pharmacology, Faculty of Science and Engineering, Groningen Research Institute of Pharmacy (GRIP), University of Groningen, 9713 AV Groningen, The NetherlandsDepartment of Molecular Pharmacology, Faculty of Science and Engineering, Groningen Research Institute of Pharmacy (GRIP), University of Groningen, 9713 AV Groningen, The NetherlandsDepartment of Molecular Pharmacology, Faculty of Science and Engineering, Groningen Research Institute of Pharmacy (GRIP), University of Groningen, 9713 AV Groningen, The NetherlandsDepartment of Cell Biochemistry, Groningen Institute of Biomolecular Sciences & Biotechnology (GBB), University of Groningen, 9747 AG Groningen, The NetherlandsDepartment of Molecular Pharmacology, Faculty of Science and Engineering, Groningen Research Institute of Pharmacy (GRIP), University of Groningen, 9713 AV Groningen, The NetherlandsDepartment of Cell Biochemistry, Groningen Institute of Biomolecular Sciences & Biotechnology (GBB), University of Groningen, 9747 AG Groningen, The NetherlandsDepartment of Molecular Pharmacology, Faculty of Science and Engineering, Groningen Research Institute of Pharmacy (GRIP), University of Groningen, 9713 AV Groningen, The NetherlandsDysfunction of the immune system and mitochondrial metabolism has been associated with Parkinson’s disease (PD) pathology. Mutations and increased kinase activity of leucine-rich repeat kinase 2 (LRRK2) are linked to both idiopathic and familial PD. However, the function of LRRK2 in the immune cells under inflammatory conditions is contradictory. Our results showed that lipopolysaccharide (LPS) stimulation increased the kinase activity of LRRK2 in parental RAW 264.7 (WT) cells. In addition to this, LRRK2 deletion in LRRK2 KO RAW 264.7 (KO) cells altered cell morphology following LPS stimulation compared to the WT cells, as shown by an increase in the cell impedance as observed by the xCELLigence measurements. LPS stimulation caused an increase in the cellular reactive oxygen species (ROS) levels in both WT and KO cells. However, WT cells displayed a higher ROS level compared to the KO cells. Moreover, <i>LRRK2</i> deletion led to a reduction in interleukin-6 (IL-6) inflammatory cytokine and cyclooxygenase-2 (COX-2) expression and an increase in lactate production after LPS stimulation compared to the WT cells. These data illustrate that LRRK2 has an effect on inflammatory processes in RAW macrophages upon LPS stimulation.https://www.mdpi.com/1422-0067/24/2/1644LRRK2inflammationLPScytokines |
| spellingShingle | Asmaa Oun Emmy Hoeksema Ahmed Soliman Famke Brouwer Fabiola García-Reyes Henderikus Pots Marina Trombetta-Lima Arjan Kortholt Amalia M. Dolga Characterization of Lipopolysaccharide Effects on LRRK2 Signaling in RAW Macrophages International Journal of Molecular Sciences LRRK2 inflammation LPS cytokines |
| title | Characterization of Lipopolysaccharide Effects on LRRK2 Signaling in RAW Macrophages |
| title_full | Characterization of Lipopolysaccharide Effects on LRRK2 Signaling in RAW Macrophages |
| title_fullStr | Characterization of Lipopolysaccharide Effects on LRRK2 Signaling in RAW Macrophages |
| title_full_unstemmed | Characterization of Lipopolysaccharide Effects on LRRK2 Signaling in RAW Macrophages |
| title_short | Characterization of Lipopolysaccharide Effects on LRRK2 Signaling in RAW Macrophages |
| title_sort | characterization of lipopolysaccharide effects on lrrk2 signaling in raw macrophages |
| topic | LRRK2 inflammation LPS cytokines |
| url | https://www.mdpi.com/1422-0067/24/2/1644 |
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