TNF-α/TNFR1 regulates the polarization of Kupffer cells to mediate trichloroethylene-induced liver injury
We have previously shown trichloroethylene (TCE) induced immune liver injury, and TNF-α/TNFR1 pathway as a probably mechanism underlying the immune damage, but the pathogenic mechanism is still unclear. The study aims to investigate whether TNF-α and its receptors regulate Kupffer cell polarization...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-01-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651321012537 |
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| author | Jia-xiang Zhang Yi Yang Hua Huang Hai-bo Xie Meng Huang Wei Jiang Bai-wang Ding Qi-xing Zhu |
| author_facet | Jia-xiang Zhang Yi Yang Hua Huang Hai-bo Xie Meng Huang Wei Jiang Bai-wang Ding Qi-xing Zhu |
| author_sort | Jia-xiang Zhang |
| collection | DOAJ |
| description | We have previously shown trichloroethylene (TCE) induced immune liver injury, and TNF-α/TNFR1 pathway as a probably mechanism underlying the immune damage, but the pathogenic mechanism is still unclear. The study aims to investigate whether TNF-α and its receptors regulate Kupffer cell polarization and downstream inflammation signaling pathways during TCE sensitization, to clarify the mechanism of TCE-mediated immune liver injury. 6–8 weeks old SPF BALB/c female mice were used to establish a TCE sensitization model. We found that in the TCE sensitization positive group, liver injury was aggravated, Kupffer cells activated and polarized to M1 type. The expression of M1 Kupffer cell marker proteins CD11c and CD16/32 increased in the TCE positive group, so did TNF-α and TNFR1 in liver. The expression of P-IKK protein, PP65 protein and P-STAT3 protein increased in the TCE sensitization positive group, and the downstream inflammatory factors IL-1β and IL-6 also increased in the TCE sensitization positive group. After using the TNFR1 inhibitor R7050, we found that M1 Kupffer cell polarization, TNF-α expression, signal pathway expression and inflammatory factors IL-1β and IL-6 expression declined, and the liver damage relieved. Briefly, the use of R7050 to inhibit TNF-α/TNFR1 changing the polarization of liver M1 Kupffer cell, thereby inhibiting the activation of related downstream signaling pathways and reducing the secretion of inflammatory factors. TNF-α/TNFR1 regulates the polarization of M1 Kupffer cells inflammatory play an important role in liver immune damage. |
| first_indexed | 2024-04-11T18:22:29Z |
| format | Article |
| id | doaj.art-cb3d1e57ba3446ab8a95a033043d2522 |
| institution | Directory Open Access Journal |
| issn | 0147-6513 |
| language | English |
| last_indexed | 2024-04-11T18:22:29Z |
| publishDate | 2022-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj.art-cb3d1e57ba3446ab8a95a033043d25222022-12-22T04:09:44ZengElsevierEcotoxicology and Environmental Safety0147-65132022-01-01230113141TNF-α/TNFR1 regulates the polarization of Kupffer cells to mediate trichloroethylene-induced liver injuryJia-xiang Zhang0Yi Yang1Hua Huang2Hai-bo Xie3Meng Huang4Wei Jiang5Bai-wang Ding6Qi-xing Zhu7Department of Occupational Health and Environmental Health, School of Public Health, Anhui Medical University, Hefei, Anhui, China; Institute of Dermatology, Key Laboratory of Dermatology, Ministry of Education, Hefei, Anhui, ChinaDepartment of Occupational Health and Environmental Health, School of Public Health, Anhui Medical University, Hefei, Anhui, ChinaDepartment of Occupational Health and Environmental Health, School of Public Health, Anhui Medical University, Hefei, Anhui, ChinaInstitute of Dermatology, Key Laboratory of Dermatology, Ministry of Education, Hefei, Anhui, China; Department of dermatological, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, ChinaDepartment of Occupational Health and Environmental Health, School of Public Health, Anhui Medical University, Hefei, Anhui, ChinaDepartment of Occupational Health and Environmental Health, School of Public Health, Anhui Medical University, Hefei, Anhui, ChinaDepartment of Occupational Health and Environmental Health, School of Public Health, Anhui Medical University, Hefei, Anhui, ChinaInstitute of Dermatology, Key Laboratory of Dermatology, Ministry of Education, Hefei, Anhui, China; Department of dermatological, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China; Correspondence to: Institute of Dermatology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.We have previously shown trichloroethylene (TCE) induced immune liver injury, and TNF-α/TNFR1 pathway as a probably mechanism underlying the immune damage, but the pathogenic mechanism is still unclear. The study aims to investigate whether TNF-α and its receptors regulate Kupffer cell polarization and downstream inflammation signaling pathways during TCE sensitization, to clarify the mechanism of TCE-mediated immune liver injury. 6–8 weeks old SPF BALB/c female mice were used to establish a TCE sensitization model. We found that in the TCE sensitization positive group, liver injury was aggravated, Kupffer cells activated and polarized to M1 type. The expression of M1 Kupffer cell marker proteins CD11c and CD16/32 increased in the TCE positive group, so did TNF-α and TNFR1 in liver. The expression of P-IKK protein, PP65 protein and P-STAT3 protein increased in the TCE sensitization positive group, and the downstream inflammatory factors IL-1β and IL-6 also increased in the TCE sensitization positive group. After using the TNFR1 inhibitor R7050, we found that M1 Kupffer cell polarization, TNF-α expression, signal pathway expression and inflammatory factors IL-1β and IL-6 expression declined, and the liver damage relieved. Briefly, the use of R7050 to inhibit TNF-α/TNFR1 changing the polarization of liver M1 Kupffer cell, thereby inhibiting the activation of related downstream signaling pathways and reducing the secretion of inflammatory factors. TNF-α/TNFR1 regulates the polarization of M1 Kupffer cells inflammatory play an important role in liver immune damage.http://www.sciencedirect.com/science/article/pii/S0147651321012537TrichloroethyleneLiver injuryTNF-αKupffer cell |
| spellingShingle | Jia-xiang Zhang Yi Yang Hua Huang Hai-bo Xie Meng Huang Wei Jiang Bai-wang Ding Qi-xing Zhu TNF-α/TNFR1 regulates the polarization of Kupffer cells to mediate trichloroethylene-induced liver injury Ecotoxicology and Environmental Safety Trichloroethylene Liver injury TNF-α Kupffer cell |
| title | TNF-α/TNFR1 regulates the polarization of Kupffer cells to mediate trichloroethylene-induced liver injury |
| title_full | TNF-α/TNFR1 regulates the polarization of Kupffer cells to mediate trichloroethylene-induced liver injury |
| title_fullStr | TNF-α/TNFR1 regulates the polarization of Kupffer cells to mediate trichloroethylene-induced liver injury |
| title_full_unstemmed | TNF-α/TNFR1 regulates the polarization of Kupffer cells to mediate trichloroethylene-induced liver injury |
| title_short | TNF-α/TNFR1 regulates the polarization of Kupffer cells to mediate trichloroethylene-induced liver injury |
| title_sort | tnf α tnfr1 regulates the polarization of kupffer cells to mediate trichloroethylene induced liver injury |
| topic | Trichloroethylene Liver injury TNF-α Kupffer cell |
| url | http://www.sciencedirect.com/science/article/pii/S0147651321012537 |
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