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Article: Major histocompatibility complexes are up-regulated in glomerular endothelial cells via activation of c-Jun N-terminal kinase in 5/6 nephrectomy mice
Title | Major histocompatibility complexes are up-regulated in glomerular endothelial cells via activation of c-Jun N-terminal kinase in 5/6 nephrectomy mice |
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Authors | |
Keywords | glomerular endothelial cell IFN-gamma JNK major histocompatibility complex MHC Class II transactivator |
Issue Date | 2020 |
Publisher | John Wiley & Sons Ltd. The Journal's web site is located at http://www.wiley.com/bw/journal.asp?ref=0007-1188&site=1 |
Citation | British Journal of Pharmacology, 2020, v. 177 n. 22, p. 5131-5147 How to Cite? |
Abstract | Background and Purpose: This study aims to explore the mechanism underlying the up-regulation of major histocompatibility complex (MHC) proteins in glomerular endothelial cells in 5/6 nephrectomy mice.
Experimental Approach: C57/BL6 mice were randomly allocated to sham-operated (2K) and 5/6 nephrectomy (5/6Nx) groups. Mouse splenic lymphocytes, from either syngeneic or allogeneic background, were injected into 5/6Nx mice after total body irradiation. Human glomerular endothelial cells (HGECs) were cultured for experiments in vitro. Western blots, PCR, immunohistochemical and fluorescent staining were used, along with assays of tissue cytokines, lymphocyte migration and renal function.
Key Results: Four weeks after nephrectomy, expression of both mRNA and protein of MHC II, CD80, and CD86 were increased in 5/6Nx glomerular endothelial cells. After total body irradiation, 5/6Nx mice injected with lymphocytes from Balb/c mice, but not those from C57/BL6 mice, exhibited increased creatinine levels, indicating that allograft lymphocyte transfer impaired renal function. In HGECs, the protein levels of MHC and MHC Class II transactivator (CIITA) were increased by stimulation with TNF-alpha or IFN-gamma, which promoted human lymphocytes movement. These increases were reduced by JNK inhibitors. In the 5/6Nx mice, JNK inhibition down-regulated MHC II protein in glomerular endothelial cells, suggesting that JNK signalling participates in the regulation of MHC II protein.
Conclusion and Implications: Chronic inflammation in mice subjected to nephrectomy induces the up-regulation of MHC molecules in glomerular endothelial cells. This up-regulation is reduced by inhibition of JNK signalling. |
Persistent Identifier | http://hdl.handle.net/10722/305022 |
ISSN | 2023 Impact Factor: 6.8 2023 SCImago Journal Rankings: 2.119 |
PubMed Central ID | |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Zhu, D | - |
dc.contributor.author | Tang, Q | - |
dc.contributor.author | Yu, B | - |
dc.contributor.author | Meng, M | - |
dc.contributor.author | Liu, W | - |
dc.contributor.author | Li, J | - |
dc.contributor.author | Zhu, T | - |
dc.contributor.author | Vanhoutte, PM | - |
dc.contributor.author | Leung, SWS | - |
dc.contributor.author | Zhang, Y | - |
dc.contributor.author | Shi, Y | - |
dc.date.accessioned | 2021-10-05T02:38:38Z | - |
dc.date.available | 2021-10-05T02:38:38Z | - |
dc.date.issued | 2020 | - |
dc.identifier.citation | British Journal of Pharmacology, 2020, v. 177 n. 22, p. 5131-5147 | - |
dc.identifier.issn | 0007-1188 | - |
dc.identifier.uri | http://hdl.handle.net/10722/305022 | - |
dc.description.abstract | Background and Purpose: This study aims to explore the mechanism underlying the up-regulation of major histocompatibility complex (MHC) proteins in glomerular endothelial cells in 5/6 nephrectomy mice. Experimental Approach: C57/BL6 mice were randomly allocated to sham-operated (2K) and 5/6 nephrectomy (5/6Nx) groups. Mouse splenic lymphocytes, from either syngeneic or allogeneic background, were injected into 5/6Nx mice after total body irradiation. Human glomerular endothelial cells (HGECs) were cultured for experiments in vitro. Western blots, PCR, immunohistochemical and fluorescent staining were used, along with assays of tissue cytokines, lymphocyte migration and renal function. Key Results: Four weeks after nephrectomy, expression of both mRNA and protein of MHC II, CD80, and CD86 were increased in 5/6Nx glomerular endothelial cells. After total body irradiation, 5/6Nx mice injected with lymphocytes from Balb/c mice, but not those from C57/BL6 mice, exhibited increased creatinine levels, indicating that allograft lymphocyte transfer impaired renal function. In HGECs, the protein levels of MHC and MHC Class II transactivator (CIITA) were increased by stimulation with TNF-alpha or IFN-gamma, which promoted human lymphocytes movement. These increases were reduced by JNK inhibitors. In the 5/6Nx mice, JNK inhibition down-regulated MHC II protein in glomerular endothelial cells, suggesting that JNK signalling participates in the regulation of MHC II protein. Conclusion and Implications: Chronic inflammation in mice subjected to nephrectomy induces the up-regulation of MHC molecules in glomerular endothelial cells. This up-regulation is reduced by inhibition of JNK signalling. | - |
dc.language | eng | - |
dc.publisher | John Wiley & Sons Ltd. The Journal's web site is located at http://www.wiley.com/bw/journal.asp?ref=0007-1188&site=1 | - |
dc.relation.ispartof | British Journal of Pharmacology | - |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.subject | glomerular endothelial cell | - |
dc.subject | IFN-gamma | - |
dc.subject | JNK | - |
dc.subject | major histocompatibility complex | - |
dc.subject | MHC Class II transactivator | - |
dc.title | Major histocompatibility complexes are up-regulated in glomerular endothelial cells via activation of c-Jun N-terminal kinase in 5/6 nephrectomy mice | - |
dc.type | Article | - |
dc.identifier.email | Leung, SWS: swsleung@hku.hk | - |
dc.identifier.authority | Vanhoutte, PM=rp00238 | - |
dc.identifier.authority | Leung, SWS=rp00235 | - |
dc.description.nature | published_or_final_version | - |
dc.identifier.doi | 10.1111/bph.15237 | - |
dc.identifier.pmid | 32830316 | - |
dc.identifier.pmcid | PMC7589013 | - |
dc.identifier.scopus | eid_2-s2.0-85091727991 | - |
dc.identifier.hkuros | 326142 | - |
dc.identifier.volume | 177 | - |
dc.identifier.issue | 22 | - |
dc.identifier.spage | 5131 | - |
dc.identifier.epage | 5147 | - |
dc.identifier.isi | WOS:000573774200001 | - |
dc.publisher.place | United Kingdom | - |