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Article: Polymeric IgA increases the synthesis of macrophage migration inhibitory factor by human mesangial cells in IgA nephropathy

TitlePolymeric IgA increases the synthesis of macrophage migration inhibitory factor by human mesangial cells in IgA nephropathy
Authors
KeywordsIgA nephropathy
IgA1
Macrophage migration inhibitory factor
Mesangial cells
Polymeric IgA
Tumour necrosis factor-α
Issue Date2003
PublisherOxford University Press. The Journal's web site is located at http://ndt.oxfordjournals.org/
Citation
Nephrology Dialysis Transplantation, 2003, v. 18 n. 1, p. 36-45 How to Cite?
AbstractBackground. It has been suggested that polymeric IgA (pIgA) or IgA immune complexes play a significant pathogenic role in IgA nephropathy (IgAN). Macrophage migration inhibitory factor (MIF) shares many activities with other pro-inflammatory cytokines. In human glomerulonephritis, including IgAN, glomerular expression of MIF is found to correlate with progressive renal injury. We hypothesized that deposition of pIgA within the kidney may lead to enhanced synthesis of MIF by mesangial cells. Methods. In this study we examined the effect of pIgA and monomeric IgA (mIgA) from randomly selected patients with IgAN in clinical quiescence on the gene expression and protein synthesis of MIF in cultured human mesangial cells (HMC). Results. Both pIgA and mIgA from IgAN patients or matched healthy controls increased MIF gene expression and protein synthesis in a dose-dependent fashion. The magnitude of MIF protein induction by pIgA (100 μg/ml) was similar to that of tumour necrosis factor-α (TNF-α) at 10 pg/ml. In all subjects, the induction of MIF was higher for pIgA when compared with mIgA (P<0.01). Furthermore, the up-regulation of MIF synthesis by either pIgA or mIgA was significantly higher in IgAN patients than in healthy controls (P < 0.05). Similarly, pIgA and mIgA were able to induce TNF-α gene expression and protein synthesis in mesangial cells. Incubation of mesangial cells with neutralizing antibody to TNF-α reduced the MIF synthesis induced by pIgA. Conclusion. We demonstrate that pIgA is capable of inducing MIF and TNF-α production in HMC, which may play a major pathogenic role in IgAN. Induction of MIF can be partially blocked by neutralizing antibody to TNF-α, suggesting the possibility that up-regulation of MIF synthesis in HMC is mediated via an amplifying proinflammatory loop involving TNF-α.
Persistent Identifierhttp://hdl.handle.net/10722/162666
ISSN
2015 Impact Factor: 4.085
2015 SCImago Journal Rankings: 1.780
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLeung, JCKen_HK
dc.contributor.authorTang, SCWen_HK
dc.contributor.authorChan, LYYen_HK
dc.contributor.authorTsang, AWLen_HK
dc.contributor.authorLan, HYen_HK
dc.contributor.authorLai, KNen_HK
dc.date.accessioned2012-09-05T05:22:11Z-
dc.date.available2012-09-05T05:22:11Z-
dc.date.issued2003en_HK
dc.identifier.citationNephrology Dialysis Transplantation, 2003, v. 18 n. 1, p. 36-45en_HK
dc.identifier.issn0931-0509en_HK
dc.identifier.urihttp://hdl.handle.net/10722/162666-
dc.description.abstractBackground. It has been suggested that polymeric IgA (pIgA) or IgA immune complexes play a significant pathogenic role in IgA nephropathy (IgAN). Macrophage migration inhibitory factor (MIF) shares many activities with other pro-inflammatory cytokines. In human glomerulonephritis, including IgAN, glomerular expression of MIF is found to correlate with progressive renal injury. We hypothesized that deposition of pIgA within the kidney may lead to enhanced synthesis of MIF by mesangial cells. Methods. In this study we examined the effect of pIgA and monomeric IgA (mIgA) from randomly selected patients with IgAN in clinical quiescence on the gene expression and protein synthesis of MIF in cultured human mesangial cells (HMC). Results. Both pIgA and mIgA from IgAN patients or matched healthy controls increased MIF gene expression and protein synthesis in a dose-dependent fashion. The magnitude of MIF protein induction by pIgA (100 μg/ml) was similar to that of tumour necrosis factor-α (TNF-α) at 10 pg/ml. In all subjects, the induction of MIF was higher for pIgA when compared with mIgA (P<0.01). Furthermore, the up-regulation of MIF synthesis by either pIgA or mIgA was significantly higher in IgAN patients than in healthy controls (P < 0.05). Similarly, pIgA and mIgA were able to induce TNF-α gene expression and protein synthesis in mesangial cells. Incubation of mesangial cells with neutralizing antibody to TNF-α reduced the MIF synthesis induced by pIgA. Conclusion. We demonstrate that pIgA is capable of inducing MIF and TNF-α production in HMC, which may play a major pathogenic role in IgAN. Induction of MIF can be partially blocked by neutralizing antibody to TNF-α, suggesting the possibility that up-regulation of MIF synthesis in HMC is mediated via an amplifying proinflammatory loop involving TNF-α.en_HK
dc.languageengen_US
dc.publisherOxford University Press. The Journal's web site is located at http://ndt.oxfordjournals.org/en_HK
dc.relation.ispartofNephrology Dialysis Transplantationen_HK
dc.subjectIgA nephropathyen_HK
dc.subjectIgA1en_HK
dc.subjectMacrophage migration inhibitory factoren_HK
dc.subjectMesangial cellsen_HK
dc.subjectPolymeric IgAen_HK
dc.subjectTumour necrosis factor-αen_HK
dc.subject.meshAdulten_US
dc.subject.meshBase Sequenceen_US
dc.subject.meshDna Primersen_US
dc.subject.meshFemaleen_US
dc.subject.meshGene Expression Regulation - Immunologyen_US
dc.subject.meshGlomerular Mesangium - Blood Supply - Immunology - Pathologyen_US
dc.subject.meshGlomerulonephritis, Iga - Genetics - Pathology - Therapyen_US
dc.subject.meshHumansen_US
dc.subject.meshImmunoglobulin A - Blood - Therapeutic Useen_US
dc.subject.meshMacrophage Migration-Inhibitory Factors - Geneticsen_US
dc.subject.meshMaleen_US
dc.subject.meshProteinuria - Etiologyen_US
dc.subject.meshRecombinant Proteins - Therapeutic Useen_US
dc.subject.meshReference Valuesen_US
dc.subject.meshTumor Necrosis Factor-Alpha - Genetics - Therapeutic Useen_US
dc.titlePolymeric IgA increases the synthesis of macrophage migration inhibitory factor by human mesangial cells in IgA nephropathyen_HK
dc.typeArticleen_HK
dc.identifier.emailLeung, JCK: jckleung@hku.hken_HK
dc.identifier.emailTang, SCW: scwtang@hku.hken_HK
dc.identifier.emailLai, KN: knlai@hku.hken_HK
dc.identifier.authorityLeung, JCK=rp00448en_HK
dc.identifier.authorityTang, SCW=rp00480en_HK
dc.identifier.authorityLai, KN=rp00324en_HK
dc.description.naturelink_to_OA_fulltexten_US
dc.identifier.doi10.1093/ndt/18.1.36en_HK
dc.identifier.pmid12480958-
dc.identifier.scopuseid_2-s2.0-0037231850en_HK
dc.identifier.hkuros81135-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0037231850&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume18en_HK
dc.identifier.issue1en_HK
dc.identifier.spage36en_HK
dc.identifier.epage45en_HK
dc.identifier.isiWOS:000180293800009-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridLeung, JCK=7202180349en_HK
dc.identifier.scopusauthoridTang, SCW=7403437082en_HK
dc.identifier.scopusauthoridChan, LYY=8108378300en_HK
dc.identifier.scopusauthoridTsang, AWL=7006979244en_HK
dc.identifier.scopusauthoridLan, HY=7102710832en_HK
dc.identifier.scopusauthoridLai, KN=7402135706en_HK

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