Toxic effects of permethrin on HMC3 microglia and its associated mechanism
BackgroundPermethrin is a commonly used pyrethroid insecticide and has been found to be potentially neurotoxic. Microglia are innate immune cells in the central nervous system and are involved in the development of a range of neurodegenerative diseases. ObjectiveTo observe possible toxic effects of...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Editorial Committee of Journal of Environmental and Occupational Medicine
2024-03-01
|
| Series: | 环境与职业医学 |
| Subjects: | |
| Online Access: | http://www.jeom.org/article/cn/10.11836/JEOM23269 |
| _version_ | 1797220116803354624 |
|---|---|
| author | Wanli ZHANG Wenqi SHAN Chao CHEN Haowei DONG Hao YUAN Qiuming ZHOU Feng TAO Heng PENG Yajun MA |
| author_facet | Wanli ZHANG Wenqi SHAN Chao CHEN Haowei DONG Hao YUAN Qiuming ZHOU Feng TAO Heng PENG Yajun MA |
| author_sort | Wanli ZHANG |
| collection | DOAJ |
| description | BackgroundPermethrin is a commonly used pyrethroid insecticide and has been found to be potentially neurotoxic. Microglia are innate immune cells in the central nervous system and are involved in the development of a range of neurodegenerative diseases. ObjectiveTo observe possible toxic effects of permethrin on human microglia clone 3 (HMC3) in vitro and explore associated mechanism. MethodsHMC3 were treated with 0, 10, 25, and 55 μmol·L−1 permethrin for 72 h. Cell cycle and apoptosis were measured using flow cytometry. Cyclin-dependent kinase 1 (CDK1), cyclin-dependent kinase inhibitor 1A (CDKN1A), cyclin B2 (CCNB2), cellular tumor antigen p53 (p53), factor-related apoptosis (FAS), caspase 3 (CASP3), and H2A histone family member X (H2AX) were detected by quantitative real-time PCR (qPCR). The differential genes and enrichment pathways of HMC3 after 0 and 25 μmol·L−1 permethrin treatment was analyzed by RNA sequencing. HMC3 was treated by 0, 10, 25, and 55 μmol· L−1 permethrin for 72 h. The content of nitric oxide (NO) in the supernatant was detected using Griess reagent. The secretion level of interleukin-6 (IL-6) was detected by enzyme linked immunosorbent assay (ELISA). The mRNA expression levels of mitogen-activated protein kinase (MAPK) pathway (including MAPK1, MAPK8, and MAPK14), interleukin-1β (IL-1β), IL-6, and matrix metalloproteinase (MMP) families (including MMP1, MMP2, MMP3, and MMP9) were detected by qPCR. The protein expressions of phosphorylated p38 mitogen-activated protein kinase (p-p38), phosphorylated extracellular signal-regulated kinase (p-ERK), IL-1β, IL-6, and MMP1 were detected by Western blot. ResultsHMC3 was arrested in G2/M phase after 0, 10, 25, and 55 μmol·L−1 permethrin treatment for 72 h, of which there was a statistically significant difference between the 55 μmol·L−1 permethrin treatment group and the control group (P<0.01), and the mRNA expression of CDKN1A was up-regulated according to the qPCR (P<0.05). There was no statistically significant difference in the proportions of apoptosis between the groups (P＞0.05). The RNA sequencing showed that the differential genes were enriched in the MAPK pathway, and the mRNA expressions of MAPK1, MAPK8, and MAPK14 were up-regulated after the permethrin treatment at 55 μmol·L−1 compared to the control group by qPCR (P<0.05). The Western blot revealed that, compared to the control group, the levels of p-p38 and p-ERK were increased after the 10 μmol·L−1 permetrin treatment (P<0.05), the p-ERK level was increased after the 25 μmol·L−1 permetrin treatment (P<0.05), and the p-p38 level was up-regulated after the 55 μmol·L−1 permetrin treatment (P<0.05). The secretion of NO in the supernatant of HMC3 increased after permetrin treatment compared to the control group (P<0.05), the mRNA and protein expressions and the secretion of IL-6 showed an upward trend, the mRNA and protein expressions of IL-1β were up-regulated (P<0.05), and the mRNA and protein expressions of MMP1 were up-regulated in the 25 and 55 μmol·L−1 permethrin groups (P<0.05). ConclusionPermethrin inhibits HMC3 cell proliferation in vitro, induces cell cycle arrest, activates MAPK pathway, and promotes the expression of inflammatory factors IL-1β and MMP1, which may be one of the mechanism of neurotoxicity induced by permethrin. |
| first_indexed | 2024-04-24T12:44:26Z |
| format | Article |
| id | doaj.art-1eb8c290c1314187973b32615de765a8 |
| institution | Directory Open Access Journal |
| issn | 2095-9982 |
| language | English |
| last_indexed | 2024-04-24T12:44:26Z |
| publishDate | 2024-03-01 |
| publisher | Editorial Committee of Journal of Environmental and Occupational Medicine |
| record_format | Article |
| series | 环境与职业医学 |
| spelling | doaj.art-1eb8c290c1314187973b32615de765a82024-04-07T06:51:56ZengEditorial Committee of Journal of Environmental and Occupational Medicine环境与职业医学2095-99822024-03-0141326727510.11836/JEOM2326923269Toxic effects of permethrin on HMC3 microglia and its associated mechanismWanli ZHANG0Wenqi SHAN1Chao CHEN2Haowei DONG3Hao YUAN4Qiuming ZHOU5Feng TAO6Heng PENG7Yajun MA8Naval Medical University Faculty of Naval MedicineNaval Medical University Faculty of Naval MedicineNaval Medical University College of Basic Medicine, Naval Medical University, Shanghai 200433, ChinaNaval Medical University College of Basic Medicine, Naval Medical University, Shanghai 200433, ChinaNaval Medical University Faculty of Naval MedicineNaval Medical University Faculty of Naval MedicineNaval Medical University Faculty of Naval MedicineNaval Medical University College of Basic Medicine, Naval Medical University, Shanghai 200433, ChinaNaval Medical University Faculty of Naval MedicineBackgroundPermethrin is a commonly used pyrethroid insecticide and has been found to be potentially neurotoxic. Microglia are innate immune cells in the central nervous system and are involved in the development of a range of neurodegenerative diseases. ObjectiveTo observe possible toxic effects of permethrin on human microglia clone 3 (HMC3) in vitro and explore associated mechanism. MethodsHMC3 were treated with 0, 10, 25, and 55 μmol·L−1 permethrin for 72 h. Cell cycle and apoptosis were measured using flow cytometry. Cyclin-dependent kinase 1 (CDK1), cyclin-dependent kinase inhibitor 1A (CDKN1A), cyclin B2 (CCNB2), cellular tumor antigen p53 (p53), factor-related apoptosis (FAS), caspase 3 (CASP3), and H2A histone family member X (H2AX) were detected by quantitative real-time PCR (qPCR). The differential genes and enrichment pathways of HMC3 after 0 and 25 μmol·L−1 permethrin treatment was analyzed by RNA sequencing. HMC3 was treated by 0, 10, 25, and 55 μmol· L−1 permethrin for 72 h. The content of nitric oxide (NO) in the supernatant was detected using Griess reagent. The secretion level of interleukin-6 (IL-6) was detected by enzyme linked immunosorbent assay (ELISA). The mRNA expression levels of mitogen-activated protein kinase (MAPK) pathway (including MAPK1, MAPK8, and MAPK14), interleukin-1β (IL-1β), IL-6, and matrix metalloproteinase (MMP) families (including MMP1, MMP2, MMP3, and MMP9) were detected by qPCR. The protein expressions of phosphorylated p38 mitogen-activated protein kinase (p-p38), phosphorylated extracellular signal-regulated kinase (p-ERK), IL-1β, IL-6, and MMP1 were detected by Western blot. ResultsHMC3 was arrested in G2/M phase after 0, 10, 25, and 55 μmol·L−1 permethrin treatment for 72 h, of which there was a statistically significant difference between the 55 μmol·L−1 permethrin treatment group and the control group (P<0.01), and the mRNA expression of CDKN1A was up-regulated according to the qPCR (P<0.05). There was no statistically significant difference in the proportions of apoptosis between the groups (P＞0.05). The RNA sequencing showed that the differential genes were enriched in the MAPK pathway, and the mRNA expressions of MAPK1, MAPK8, and MAPK14 were up-regulated after the permethrin treatment at 55 μmol·L−1 compared to the control group by qPCR (P<0.05). The Western blot revealed that, compared to the control group, the levels of p-p38 and p-ERK were increased after the 10 μmol·L−1 permetrin treatment (P<0.05), the p-ERK level was increased after the 25 μmol·L−1 permetrin treatment (P<0.05), and the p-p38 level was up-regulated after the 55 μmol·L−1 permetrin treatment (P<0.05). The secretion of NO in the supernatant of HMC3 increased after permetrin treatment compared to the control group (P<0.05), the mRNA and protein expressions and the secretion of IL-6 showed an upward trend, the mRNA and protein expressions of IL-1β were up-regulated (P<0.05), and the mRNA and protein expressions of MMP1 were up-regulated in the 25 and 55 μmol·L−1 permethrin groups (P<0.05). ConclusionPermethrin inhibits HMC3 cell proliferation in vitro, induces cell cycle arrest, activates MAPK pathway, and promotes the expression of inflammatory factors IL-1β and MMP1, which may be one of the mechanism of neurotoxicity induced by permethrin.http://www.jeom.org/article/cn/10.11836/JEOM23269permethrinmicrogliainterleukin-1βmatrix metalloproteinasemitogen-activated protein kinaseinflammatory response |
| spellingShingle | Wanli ZHANG Wenqi SHAN Chao CHEN Haowei DONG Hao YUAN Qiuming ZHOU Feng TAO Heng PENG Yajun MA Toxic effects of permethrin on HMC3 microglia and its associated mechanism 环境与职业医学 permethrin microglia interleukin-1β matrix metalloproteinase mitogen-activated protein kinase inflammatory response |
| title | Toxic effects of permethrin on HMC3 microglia and its associated mechanism |
| title_full | Toxic effects of permethrin on HMC3 microglia and its associated mechanism |
| title_fullStr | Toxic effects of permethrin on HMC3 microglia and its associated mechanism |
| title_full_unstemmed | Toxic effects of permethrin on HMC3 microglia and its associated mechanism |
| title_short | Toxic effects of permethrin on HMC3 microglia and its associated mechanism |
| title_sort | toxic effects of permethrin on hmc3 microglia and its associated mechanism |
| topic | permethrin microglia interleukin-1β matrix metalloproteinase mitogen-activated protein kinase inflammatory response |
| url | http://www.jeom.org/article/cn/10.11836/JEOM23269 |
| work_keys_str_mv | AT wanlizhang toxiceffectsofpermethrinonhmc3microgliaanditsassociatedmechanism AT wenqishan toxiceffectsofpermethrinonhmc3microgliaanditsassociatedmechanism AT chaochen toxiceffectsofpermethrinonhmc3microgliaanditsassociatedmechanism AT haoweidong toxiceffectsofpermethrinonhmc3microgliaanditsassociatedmechanism AT haoyuan toxiceffectsofpermethrinonhmc3microgliaanditsassociatedmechanism AT qiumingzhou toxiceffectsofpermethrinonhmc3microgliaanditsassociatedmechanism AT fengtao toxiceffectsofpermethrinonhmc3microgliaanditsassociatedmechanism AT hengpeng toxiceffectsofpermethrinonhmc3microgliaanditsassociatedmechanism AT yajunma toxiceffectsofpermethrinonhmc3microgliaanditsassociatedmechanism |