Messenger RNA expression of monocyte chemoattractant protein-1 and interleukin-6 in stone-containing kidneys.
OBJECTIVE
To investigate the intrarenal mRNA expression of monocyte chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6) in patients with nephrolithiasis, and to evaluate whether their expression is associated with renal function, as oxidative stress and inflammation are involved in the pathogenesis of nephrolithiasis.


METHODS
Renal biopsies from near the stone, and blood and 24-h urine specimens were collected from 29 patients with nephrolithiasis. Control renal tissues were taken from non-cancerous and cancerous portions of nephrectomy from six patients with renal cancers, and control 24-h urine samples were obtained from 30 healthy subjects. Corrected creatinine clearance, urinary N-acetyl-beta-glucosaminidase activity and 8-hydroxy-deoxyguanosine (8-OHdG) were determined. The mRNA expressions of MCP-1 and IL-6 in the tissues were measured by real time reverse transcription-polymerase chain reaction.


RESULTS
Patients with nephrolithiasis had significantly greater renal tubular damage and oxidative stress than the healthy controls. Intrarenal mRNA expressions of MCP-1 and IL-6 in stone-adjacent renal tissues were significantly lower than in cancerous renal tissues, but not statistically different from that in non-cancerous renal tissues. In stone-adjacent renal tissues, the mRNA level of MCP-1 was significantly higher than that of IL-6, but their expressions were significantly correlated with each other. Histological examination showed that the number of infiltrated leukocytes corresponded well with the intrarenal mRNA levels of MCP-1 and IL-6. Patients with nephrolithiasis and compromised renal function had significantly higher intrarenal mRNA levels of MCP-1 and IL-6 than those with preserved renal function. Also, the mRNA levels in patients with severe renal tubular damage were significantly greater than in those with less renal tubular damage. There was no association between intrarenal mRNA expression and urinary 8-OHdG.


CONCLUSIONS
Nephrolithiasis was associated with low-grade intrarenal inflammation. A greater intrarenal mRNA expression of MCP-1 and IL-6 was associated with enhanced renal impairment. Thus, expression of MCP-1 and IL-6, at least in part, contributed to the progression of nephrolithiasis.
Boonla
Chanchai
C
Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Hunapathed
Chanutra
C
Bovornpadungkitti
Sombat
S
Poonpirome
Kanitta
K
Tungsanga
Kriang
K
Sampatanukul
Pichet
P
Tosukhowong
Piyaratana
P
D000368:Aged; D016022:Case-Control Studies; D018932:Chemokine CCL2 / Q000378:metabolism*; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D007668:Kidney / Q000473:pathology*; D007680:Kidney Neoplasms / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009393:Nephritis / Q000473:pathology; D053040:Nephrolithiasis / Q000473:pathology*; D018384:Oxidative Stress / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D018932:Chemokine CCL2; D015850:Interleukin-6; D012333:RNA, Messenger