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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

TitleMajor histocompatibility complexes are up-regulated in glomerular endothelial cells via activation of c-Jun N-terminal kinase in 5/6 nephrectomy mice
Authors
Keywordsglomerular endothelial cell
IFN-gamma
JNK
major histocompatibility complex
MHC Class II transactivator
Issue Date2020
PublisherJohn 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?
AbstractBackground 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 Identifierhttp://hdl.handle.net/10722/305022
ISSN
2021 Impact Factor: 9.473
2020 SCImago Journal Rankings: 2.432
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorZhu, D-
dc.contributor.authorTang, Q-
dc.contributor.authorYu, B-
dc.contributor.authorMeng, M-
dc.contributor.authorLiu, W-
dc.contributor.authorLi, J-
dc.contributor.authorZhu, T-
dc.contributor.authorVanhoutte, PM-
dc.contributor.authorLeung, SWS-
dc.contributor.authorZhang, Y-
dc.contributor.authorShi, Y-
dc.date.accessioned2021-10-05T02:38:38Z-
dc.date.available2021-10-05T02:38:38Z-
dc.date.issued2020-
dc.identifier.citationBritish Journal of Pharmacology, 2020, v. 177 n. 22, p. 5131-5147-
dc.identifier.issn0007-1188-
dc.identifier.urihttp://hdl.handle.net/10722/305022-
dc.description.abstractBackground 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.languageeng-
dc.publisherJohn 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.ispartofBritish Journal of Pharmacology-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectglomerular endothelial cell-
dc.subjectIFN-gamma-
dc.subjectJNK-
dc.subjectmajor histocompatibility complex-
dc.subjectMHC Class II transactivator-
dc.titleMajor histocompatibility complexes are up-regulated in glomerular endothelial cells via activation of c-Jun N-terminal kinase in 5/6 nephrectomy mice-
dc.typeArticle-
dc.identifier.emailLeung, SWS: swsleung@hku.hk-
dc.identifier.authorityVanhoutte, PM=rp00238-
dc.identifier.authorityLeung, SWS=rp00235-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1111/bph.15237-
dc.identifier.pmid32830316-
dc.identifier.pmcidPMC7589013-
dc.identifier.scopuseid_2-s2.0-85091727991-
dc.identifier.hkuros326142-
dc.identifier.volume177-
dc.identifier.issue22-
dc.identifier.spage5131-
dc.identifier.epage5147-
dc.identifier.isiWOS:000573774200001-
dc.publisher.placeUnited Kingdom-

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