Pathogenic role of NF-kappaB activation in tubulointerstitial inflammatory lesions in human lupus nephritis. Export

@article{citeulike:3349324, abstract = {In vitro and in vivo experimental studies suggest that the transcription factor NF-kappaB plays a role in tubulointerstitial injury. We investigated possible cellular and molecular mechanisms involving NF-kappaB 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-kappaB and AP-1. Immunohistochemistry was performed to examine the expression of NF-kappaB, AP-1, and NF-kappaB regulatory proteins (IkappaB-alpha, p-IkappaB-alpha, and IKK-alpha proteins), as well as NF-kappaB and AP-1 downstream target proinflammatory molecules (ICAM-1, TNF-alpha, IL-1beta, IL-6, and GM-CSF) and NF-kappaB upstream signaling molecules (CD40 and CD40L). We observed extensive upregulation of activated NF-kappaB 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-kappaB correlated well with the degree of tubulointerstitial histopathological indices and/or renal function. Tubulointerstitial IKK-alpha expression was specifically upregulated in LN. IkappaB-alpha and p-IkappaB-alpha were detected only in interstitial cells in LN. Tubulointerstitial expression levels of NF-kappaB and AP-1 downstream inflammatory molecules and NF-kappaB 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-alpha expression and NF-kappaB 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.}, address = {Department of Pathology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.}, author = {Zheng, L. and Sinniah, R. and Hsu, S. I.}, citeulike-article-id = {3349324}, citeulike-linkout-0 = {http://dx.doi.org/10.1369/jhc.7A7368.2008}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/18285351}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=18285351}, doi = {10.1369/jhc.7A7368.2008}, issn = {0022-1554}, journal = {The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society}, keywords = {ln, nfkappab, sle}, month = {May}, number = {5}, pages = {517--529}, posted-at = {2008-09-29 00:28:58}, priority = {2}, title = {Pathogenic role of NF-kappaB activation in tubulointerstitial inflammatory lesions in human lupus nephritis.}, url = {http://dx.doi.org/10.1369/jhc.7A7368.2008}, volume = {56}, year = {2008} }

TY - JOUR ID - citeulike:3349324 L3 - citeulike-article-id:3349324 N2 - In vitro and in vivo experimental studies suggest that the transcription factor NF-kappaB plays a role in tubulointerstitial injury. We investigated possible cellular and molecular mechanisms involving NF-kappaB 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-kappaB and AP-1. Immunohistochemistry was performed to examine the expression of NF-kappaB, AP-1, and NF-kappaB regulatory proteins (IkappaB-alpha, p-IkappaB-alpha, and IKK-alpha proteins), as well as NF-kappaB and AP-1 downstream target proinflammatory molecules (ICAM-1, TNF-alpha, IL-1beta, IL-6, and GM-CSF) and NF-kappaB upstream signaling molecules (CD40 and CD40L). We observed extensive upregulation of activated NF-kappaB 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-kappaB correlated well with the degree of tubulointerstitial histopathological indices and/or renal function. Tubulointerstitial IKK-alpha expression was specifically upregulated in LN. IkappaB-alpha and p-IkappaB-alpha were detected only in interstitial cells in LN. Tubulointerstitial expression levels of NF-kappaB and AP-1 downstream inflammatory molecules and NF-kappaB 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-alpha expression and NF-kappaB 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. IS - 5 JF - The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society SN - 0022-1554 AD - Department of Pathology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. EP - 529 TI - Pathogenic role of NF-kappaB activation in tubulointerstitial inflammatory lesions in human lupus nephritis. VL - 56 SP - 517 KW - ln KW - nfkappab KW - sle AU - Zheng, L AU - Sinniah, R AU - Hsu, SI PY - 2008/05// UR - http://dx.doi.org/10.1369/jhc.7A7368.2008 ER -