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Table 3 Potential effects on the kidney of mediators released during mechanical ventilation

From: Bench-to-bedside review: Ventilation-induced renal injury through systemic mediator release - just theory or a causal relationship?

Mediator Effects on kidney References
TNF-α Stimulated expression of TGF-β, RANTES, MIP-2, MCP-2, IL-1β, TNF-α, T-cell activation 3, IL-6, phospholipase-A2, LIF. MHC-I upregulation [3740, 43]
  Leukocyte infiltration through MCSF, MCP-1, GRO-α, β, γ, ENA-78, GCP-2, IL-8, MIP-1β and 3α, RANTES, ICAM-1, VCAM-1, L-selectin [4449]
  Death receptor- and mitochondrial-mediated apoptosis and ceramide signaling. Necrosis through ROS. Downregulation of anti-apoptotic proteins. [5054, 5659]
  Production of vasoactive mediators: PAF, ET-1, PGs, adenosine, NO. Downregulation Ang-II-R [6069, 72]
  NO tubular epithelial cell shedding. Decreased proliferation of tubular and mesangial cells [73, 74]
  Increased PAI-1 gene expression, increased TF production with fibrin deposition [75, 76]
  Decreased gene expression for urea, glucose, sodium and chloride transporters/channels [7780]
  Decreased gene expression of nuclear hormone receptor LXR, its target genes and coactivators [81]
IL-1β Stimulated expression of IL-6, IL-8, LIF, ceramide. MHC-I upregulation [40, 43, 8789]
  Increased expression of MCP-1, GMCSF, MSF, ENA-78, RANTES, MIP-1β, ICAM-1 [9093]
  Downregulation of Ang-II-R. Expression of NO, PGE2 [39, 72, 94, 95]
  Stimulated growth of glomerular epithelial cells [96]
  Increased TF expression and activity, upregulation of tPA and PAI-1 [97, 98]
  Decreased gene expression for urea, glucose, sodium and chloride transporters/channels [7780]
  Decreased gene expression of nuclear hormone receptor LXR, its target genes and coactivators [81]
IL-6 TNF-α, IL-1β stimulation. Increased ICAM-1, P-selectin expression with neutrophil infiltration [105107]
  Increased survival, upregulation of pro- and anti-apoptotic genes [108]
  Decreased expression of Ang-II-R [72]
  Increased oxidative stress, but increased expression of HO-1, Ref-1 [105, 106]
  Proliferation of rat mesangial and tubular cells, increased HGF and met-c receptor. Conflicting reports [109111]
  Decreased gene expression for urea, glucose and chloride transporters [7779]
  Abrogation of protective effect of hyperlipidemia [115]
IL-10 Decreased synthesis of TNF-α and IL-1β [118, 119]
  Contradictory effects on ICAM-1 expression and leukocyte infiltration [118, 120]
  Prevention of apoptosis and necrosis. Decreased cell cycle activity [118]
  Reduction of VEGF, iNOS and nitrite formation [118, 121]
  Proliferation of mesangial cells [122124]
sTNFR Decreased expression of TNF-α, MCP-1 [71]
  Inhibition of apoptosis, decreased cell proliferation and fibrosis [128130]
IL-1RA Decreased gelatinase B, stromelysin, MCP-1 and IL-8 [132, 133]
  Decreased ICAM-1 expression and leukocyte infiltration [134138]
IL-8 Increased COX1 and PGE2 expression [145]
  Alterations in glomerular basement membrane sulfate metabolism [146]
MIP-2 Increased MCP-1, RANTES, MIP-2 [151]
  Decreased neutrophil influx [152, 153]
  Decreased fibrin deposition [152]
KC = GRO-α Increased MCP-1, RANTES, MIP-2, KC [151]
  Neutrophil infiltration [153]
  Stimulated proliferation of medullary collecting duct cells [154]
  Increased COX1 and PGE2 synthesis [145]
MCP-1 Increased IL-6 [155]
  Increased ICAM-1 expression, chemotaxis and haptotaxis, monocyte/macrophage infiltration [155165]
  Increased apoptosis [164]
  Increased fibrosis, TGF-β, collagen deposits [165167]
  Decreased nephrin [168]
Active PAI-1 Increased leukocyte infiltration [169]
  Fibrin, collagen deposits, increased fibronectin, TGF-β, decreased urokinase and fibrosis [169172]
tPA Conflicting reports on leukocyte infiltration [175, 178]
  Conflicting reports on fibrosis [175178]
aPC Decreased TNF-α, IL-6, IL-8, IL-18 [180182]
  Decreased KC, MIP-2, MCP-1, suppression of leukocyte rolling, adhesion and infiltration [180184]
  Decreased apoptosis, necrosis [180185]
  Decreased nitrosative stress [185]
  Decreased adrenomedullin, iNOS, angiotensin (II), ACE. Increased renal and peritubular blood flow, decreased permeability [180, 181, 184]
  Decreased extracellular matrix depositions [180, 185]
VEGF Decreased MCP-1, ICAM-1, leukocyte infiltration [188]
  Decreased apoptosis and necrosis [189192]
  Stimulated eNOS and NO expression [193, 194]
  Increased permeability [195, 196]
  Increased proliferation of glomerular cells, podocytes, mesangial cells, fibroblasts and capillaries [192, 194, 213220]
  Conflicting reports of fibrosis and sclerosis [194, 217, 219221]
  Sustained nephrin expression [221]
sFasL Increased apoptosis [10]
  1. ACE, angiotensin converting enzyme; Ang-II-R, angiotensin-II receptor; aPC, activated protein C; COX, cyclooxygenase; ENA, epithelial neutrophil activating protein; eNOS, endothelial nitric oxide synthase; ET, endothelin; GCP, granulocyte chemotactic peptide; GMCSF, granulocyte macrophage colony-stimulating factor; GRO, growth related oncogene; HGF, hepatocyte growth factor; HO, heme-oxygenase; ICAM, intercellular adhesion molecule; IL-1RA, interleukin-1 receptor antagonist; iNOS, inducible nitric oxide; KC, keratinocyte-derived chemokine; LIF, leukemia inhibitory factor; LXR, liver X receptor/retinoid X receptor; MCP, monocyte chemoattractant protein; MCSF, macrophage colony stimulating factor; MHC, major histocompatibility complex; MIP, macrophage inflammatory protein; MSF, migration stimulating factor; NO, nitric oxide; PAF, platelet activating factor; PAI, plasminogen activator inhibitor; PG, prostaglandin; RANTES, regulated upon activation, normal T-cell expressed, and secreted; Ref, restriction factor; ROS, reactive oxygen species; sFasL, soluble Fas ligand; sTNFR, soluble TNF-α receptor; TF, tissue factor; TGF, transforming growth factor; tPA, tissue type plasminogen activator; VCAM, vascular cell adhesion molecule; VEGF, vascular endothelial growth factor.