IL-12p40 and IL-18 in Crescentic Glomerulonephritis

Abstract

Experimental crescentic glomerulonephritis (GN) is

The IL-23/Th17 Axis Contributes to Renal Injury in Experimental Glomerulonephritis

“…3 This pathophysiological concept is mainly based on findings from experimental rodent models of glomerulonephritis. Renal T cell and monocyte recruitment and subsequent tissue damage are attenuated in mice with genetic deletion of Th1 cytokines such as IL-12 p40 4 and IFN␥ 5 and by blocking of Th1 cytokines with inhibitory antibodies including anti-IL-12 p40(p35) 6 and anti-IFN␥. 7 Furthermore, exogenous administration of IL-12 augments Th1 responses and crescentic glomerulonephritis.…”

IL-23, not IL-12, Directs Autoimmunity to the Goodpasture Antigen

“…IL-12, a heterodimer composed of IL-12p40 and IL-12p35 subunits, is the key cytokine in Th1 differentiation. Studies using neutralizing antibodies and IL-12p40 Ϫ/Ϫ mice, including studies in experimental glomerulonephritis, seemed to define an important role for IL-12 in both autoimmune 17 and nonautoimmune 18,19 glomerulonephritis; however, the subsequent discovery of IL-23, a newer IL-12 family member that is also a heterodimer (composed of IL-12p40 and IL23p19 subunits), prompted a reevaluation of studies that used IL-12p40 Ϫ/Ϫ mice and anti-IL-12p40 antibodies. Other lines of evidence have defined IL-23 as important for the maintenance of the Th17 subset and implicated Th17 in the pathogenesis of organ-specific autoimmune disease.…”

“…IFN-␥ and IL-4 in splenocyte supernatants were measured by ELISA, as described previously. 19,44 IL-17A, TGF-␤1, IL-12, and IL-23 were measured by ELISA: IL-17A and TGF-␤1 (R&D Systems, Minneapolis, MN) and IL-12 and IL-23 (eBioscience) as per the manufacturers' protocols. IL-6, IL-10, monocyte chemoattractant protein 1, IFN-␥, TNF, and IL-12p70 were also measured by flow cytometry using a cytometric bead array mouse inflammation kit (BD Biosciences), as per the manufacturer's protocol.…”

Role of amino acid transporter LAT2 in the activation of mTORC1 pathway and the pathogenesis of crescentic glomerulonephritis

“…[7][8][9] It is increasingly evident that proinflammatory cytokines and growth hormones released by proliferating cells in the glomerulus are involved in the pathogenesis of crescent formation. [10][11][12][13] These factors stimulate the p38 mitogen-activated protein kinase (MAPK) pathway, resulting in the production of inflammatory mediators. [14][15][16] The involvement of the MAPK pathway in the pathogenesis of CGN was first reported by Bokemeyer et al, 17 who demonstrated a rapid and sustained activation of extracellular signal-regulated kinase in the glomeruli isolated from rat model of anti-GBM nephritis.…”