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Background. Blockade of CD40–CD40 ligand (CD154) interactions protects against renal injury in adriamycin nephropathy (AN) in immunocompetent mice. To investigate whether this protection relied on adaptive or cognate immunity, we tested the effect of CD40–CD154 blockade in severe combined immunodeficient (SCID) mice. [ABSTRACT FROM PUBLISHER]

Presents the abstract 'Partial Depletion of Macrophages By ED7 Reduces Renal Injury in Adriamycin Nephropathy,' by Yiping Wang, Yuet-Ching Tay, Tim Spicer, Lucas Kairaitis, Yang Wang, Ling Zheng and David C.H. Harris.

Proximal tubule cells stimulated by lipopolysaccharide inhibit macrophage activation. Background. Tubule cells can produce a variety of cytokines, extracellular matrix (ECM) components, and adhesion molecules in vitro and in vivo. It is generally assumed that stimulated tubule cells are proinflammatory and at least partially responsible for interstitial inflammation. However, the overall effect of tubular cells on interstitial cells is unknown. In this study, pro- and anti-inflammatory cytokine production and net effects on macrophages of tubule cells activated by lipopolysaccharide (LPS) were examined. Methods. Tubule cells stimulated with LPS expressed tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-12, monocyte chemoattractant protein-1 (MCP-1), IL-10, and transforming growth factor-β (TGF-β). Conditioned media werecollected from confluent monolayers of rat tubule cells stimulated, or not, by LPS for 4 and 18 hours, respectively. Macrophages were cultured with conditioned media and/or LPS (0.5 μg/mL) for 18 hours. Results. TNF-α and IL-lβ mRNA of macrophages stimulated by LPS increased more than fivefold when cultured with control conditioned media from unstimulated tubule cells. Surprisingly, TNF-α and IL-lβ levels of macrophages stimulated by LPS were not increased when cultured with conditioned media from activated tubule cells. Neutralizing antibodies to IL-10 and TGF-β were used to define the inhibitory component(s) in conditioned medium. Anti-IL-10, but not anti-TGF-β, abolished partially the inhibitory effects of conditioned media on macrophages. Conclusion. Tubule cells produce both pro- and anti-inflammatory cytokines and the net effect, partially explained by IL-10, of tubule cells activated with LPS is to inhibit activity of macrophages. Thus, the net effect of activated tubule cells on interstitial pathology may in certain circumstances, be anti- rather than pro-inflammatory. [ABSTRACT FROM AUTHOR]

Abstract: CCL2 DNA vaccines are directed against the host chemoattractant molecule CCL2 (MCP-1), a key chemokine in recruiting macrophages to sites of inflammation. Macrophages recruited by CCL2 lead to progressive renal injury. In rat models of disease unmodified CCL2 DNA vaccine in combination with a CCL5 (RANTES) DNA vaccine can protect against chronic renal disease. The mechanism of protection involves the induction of auto-antibodies to the CCL2. Introduction of the adjuvant p-tet into the DNA structure of the CCL2 vaccine leads to enhanced potency with the induction of specific Th1 cellular immunity. The strategies outlined here demonstrate a model for developing potent vaccines against highly restricted self targets. [Copyright &y& Elsevier]