{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,3]],"date-time":"2026-05-03T23:45:07Z","timestamp":1777851907630,"version":"3.51.4"},"reference-count":54,"publisher":"SAGE Publications","issue":"5","license":[{"start":{"date-parts":[[2008,2,18]],"date-time":"2008-02-18T00:00:00Z","timestamp":1203292800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Histochem Cytochem."],"published-print":{"date-parts":[[2008,5]]},"abstract":"<jats:p>In vitro and in vivo experimental studies suggest that the transcription factor NF-\u03baB plays a role in tubulointerstitial injury. We investigated possible cellular and molecular mechanisms involving NF-\u03baB activation in the progression of tubulointerstitial lesions in human lupus nephritis (LN). Paraffin-embedded renal biopsies from 50 patients with LN and six control patients with minimal change disease (MCD) were examined by Southwestern histochemistry for in situ detection of active NF-\u03baB and AP-1. Immunohistochemistry was performed to examine the expression of NF-\u03baB, AP-1, and NF-\u03baB regulatory proteins (I\u03baB-\u03b1, p-I\u03baB-\u03b1, and IKK-\u03b1 proteins), as well as NF-\u03baB and AP-1 downstream target proinflammatory molecules (ICAM-1, TNF-\u03b1, IL-1\u03b2, IL-6, and GM-CSF) and NF-\u03baB upstream signaling molecules (CD40 and CD40L). We observed extensive upregulation of activated NF-\u03baB in renal tubular cells and interstitial cells, in parallel with overactivation of transcription factor AP-1 in LN, as compared with normal controls and MCD. Tubular expression of activated NF-\u03baB correlated well with the degree of tubulointerstitial histopathological indices and\/or renal function. Tubulointerstitial IKK-\u03b1 expression was specifically upregulated in LN. I\u03baB-\u03b1 and p-I\u03baB-\u03b1 were detected only in interstitial cells in LN. Tubulointerstitial expression levels of NF-\u03baB and AP-1 downstream inflammatory molecules and NF-\u03baB upstream signaling molecules CD40 and CD40L were markedly enhanced in LN as compared with MCD or normal controls and were associated with tubulointerstitial histopathological indices and\/or renal function. The results suggest that altered IKK-\u03b1 expression and NF-\u03baB activation along with AP-1 overexpression may play a pathogenic role in tubulointerstitial injury in human LN mediated through a network of downstream proinflammatory molecules.<\/jats:p>","DOI":"10.1369\/jhc.7a7368.2008","type":"journal-article","created":{"date-parts":[[2008,2,19]],"date-time":"2008-02-19T22:38:32Z","timestamp":1203460712000},"page":"517-529","source":"Crossref","is-referenced-by-count":49,"title":["Pathogenic Role of NF-\u03baB Activation in Tubulointerstitial Inflammatory Lesions in Human Lupus Nephritis"],"prefix":"10.1177","volume":"56","author":[{"given":"Ling","family":"Zheng","sequence":"first","affiliation":[{"name":"Department of Pathology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raja","family":"Sinniah","sequence":"additional","affiliation":[{"name":"Department of Pathology, Yong Loo Lin 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