Macrophages, monocyte chemoattractant peptide-1, and TGF-beta 1 in experimental hydronephrosis

Abstract

Early cellular and molecular derangements have been evaluated as potential pivotal factors for the late development of interstitial fibrosis after experimental hydronephrosis. In this study, we delineated the kinetics of renal cortical macrophage infiltration as well as the cortical expression of transforming growth factor-beta 1 (TGF-beta 1) and monocyte chemoattractant peptide-1 (MCP-1) at 12, 48, and 96 h after unilateral ureteral obstruction (UUO). Interstitial macrophage number in the obstructed kidney versus the contralateral unobstructed kidney (CUK) significantly increased by 12 (11.1 +/- 0.9 vs. 4.5 +/- 0.6), 48 (27.5 +/- 0.9 vs. 4.0 +/- 0.8), and 96 h (71.4 +/- 4.6 vs. 3.2 +/- 0.4) after UUO. MCP-1 mRNA was detected from 12 to 96 h in the obstructed kidney but was absent in the CUK specimens at all time points. Apical tubular MCP-1 expression, on immunolabeling, was present from 12 through 96 h after UUO in the obstructed kidney but not the CUK specimen. On Northern analysis, there were highly significant 2.6-, 5.8-, and 7.0-fold increments in renal cortical TGF-beta 1 mRNA levels at 12, 48, and 96 h, respectively, in the obstructed kidney versus the CUK specimen. Intracellular TGF-beta 1, on immunolabeling, was detected only in the obstructed kidneys of UUO rats at all three time points and was confined to peritubular cells of the renal interstitium. A significant (P < 0.005) correlation (r = 0.95) between interstitial macrophage number and cortical TGF-beta 1 mRNA levels was noted.(ABSTRACT TRUNCATED AT 250 WORDS)

AT1A-mediated activation of kidney JNK1 and SMAD2 in obstructive uropathy: preservation of kidney tissue mass using candesartan

“…Distribution and retention of these inflammatory cells are promoted by the ubiquitous adhesion molecules ICAM-1 and VCAM-1 (45). The recruited inflammatory cells, in turn, are the source of additional proinflammatory and profibrogenic cytokines, which establish a vicious cycle that leads to disordered regulation of apoptosis and proliferation and, ultimately, loss of functional parenchyma and fibrosis (9).…”

“…These hemodynamic changes are followed by the activation of a number of cytokines (6,9,20,21,36,50), some of which have been directly linked to angiotensin II, such as monocyte chemotactic protein-1 (MCP-1) (20) and transforming growth factor-␤ (TGF-␤) (22), which appears to play a key role in the genesis of the ensuing fibrosis (32). TGF-␤ signaling is initiated after ligand binding to the TGF-␤ receptor (15,33), leading to phosphorylation of SMAD2 or SMAD3 (1,47,53).…”

Current concepts in radiation enteritis and implications for future clinical trials

“…In the animal model of hydronephrosis secondary to unilateral ureteral ligation, increased expression of TGF-␤1 mRNA was observed in the renal cortex 12 hours after obstruction. 92 The enhanced level of TGF-␤1 was located in the tubules of the obstructed kidney but not in the contralateral kidney. 93 An intense infiltration of macrophages into the tubulointerstitium preceded the TGF␤1 expression, suggesting the latter cells as a possible source of TGF-␤1 stimulation.…”

“…Ramos et al 69 Human IPF ELISA, RT-PCR Increased Ziesche et al 70 Human IPF ELISA, RT-PCR Increased, inhibited by IFN-␥ Gauldie et al 72 Rat EPF IH, CGT Increased Querfeld et al 74 Human SS IH, ISH Increased Ihn et al 75 Human SS ELISA, IB Increased, inhibited by TGF-␤ Ab Oh et al 83 Rat DN NB, MLEC Increased, inhibited by TGF-␤ Ab Hong et al 86 Mouse DN IH, ISH, SH Increased Sharma et al 87 Human DN ELISA Increased, inhibited by, captopril Helmich et al 88 Human DN SEI Increased Mezzano et al 90 Human MN IH, ISH Increased Honkanen et al 91 Human MN EIA Increased Diamond et al 92 Rat ON NB, IL Increased Isaka et al 96 Rat ON IH, NB, ISH, AODN transfer Increased, inhibited by TGF-␤ AODN Kaneto et al 97 Human ON IH, RT-PCR Increased Sharma et al 100 Human CAN RT-PCR Increased Cuhaci et al 101 Human CAN IH Increased Qi et al 104 Rat LC NB, AdCAT␤-TR transfection Inhibited by AdCAT␤-TR transfection Ueno et al 105 Rat LC IF, ELISA, AdT␤-ExR Inhibited by AdT␤-ExR injection Zhang et al 106 Rat LC ELISA Increased, inhibited by IFN-␥ gene transfer Bacr et al 107 Human LC NB, IH Increased …”

Synergistic induction of monocyte chemoattractant protein‐1 (MCP‐1) by platelet‐derived growth factor and interleukin‐1

“…In the kidney, MCP-1 expression was enhanced in different animal models of experimental glomerular nephritis (e.g. [6][7][8][9]). Glomerular MCP-1 was also detectable in biopsies from patients with inflammatory or proliferative glomerulonephritis [9].…”