Pathogenic Mechanisms in the Development of Lupus Nephritis

Abstract

To probe pathogenic mechanisms involving renal injury in lupus nephritis (LN), we investigated the role of immune responses, pro-inflammatory mediators, transcription factors responsible for upregulated transcription of the pro-inflammatory markers, and apoptosis, in the development of renal injury using renal biopsies from patients with LN. Cellular immune components correlated with clinicopathological indices of renal injury, notably in the tubulointerstitium. Striking upregulation of adhesion molecules ICAM-1/VCAM-1, CD40/CD40L signaling molecules, pro-inflammatory cytokines (TNF-alpha, IL-1beta, IL-6 and GM-CSF) and activated transcription factor NF-kappaB detected by immunohistochemistry and Southwestern histochemistry in renal resident cells and inflammatory cells, correlated with clinicopathological indices. Tubulointerstitial activation of NF-kappaB paralleled expression of NF-kappaB regulatory proteinsi??i? Finally, apoptotic or proliferative activity correlated with clinicopathological indices, renal expression of activated NF-kappaB and its downstream inflammatory enzyme iNOS. This study provides evidence for cellular mechanisms of renal injury mediated by a network of pro-inflammatory mediators that are regulated by NF-kappaB.