Expression of monocyte chemotactic protein-1 precedes monocyte recruitment in a rat model of acute liver injury, and is modulated by vitamin E.
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Expression of monocyte chemotactic protein-1 precedes monocyte recruitment in a rat model of acute liver injury, and is modulated by vitamin E. / Marra, F; DeFranco, R; Grappone, C; Parola, M; Milani, S; Leonarduzzi, G; Pastacaldi, S; Wenzel, Ulrich; Pinzani, M; Dianzani, M U; Laffi, G; Gentilini, P.
In: J INVEST MED, Vol. 47, No. 1, 1, 1999, p. 66-75.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - Expression of monocyte chemotactic protein-1 precedes monocyte recruitment in a rat model of acute liver injury, and is modulated by vitamin E.
AU - Marra, F
AU - DeFranco, R
AU - Grappone, C
AU - Parola, M
AU - Milani, S
AU - Leonarduzzi, G
AU - Pastacaldi, S
AU - Wenzel, Ulrich
AU - Pinzani, M
AU - Dianzani, M U
AU - Laffi, G
AU - Gentilini, P
PY - 1999
Y1 - 1999
N2 - BACKGROUND: Increased expression of monocyte chemotactic protein-1 (MCP-1) has been indicated as a mechanism underlying leukocyte recruitment after liver injury. In this study we examined the temporal relationship between MCP-1 expression and the appearance of monocyte infiltration during acute liver injury. In addition, we tested the effects of vitamin E, a well known antioxidant, on these parameters. Rats were intoxicated with a single intragastric administration of CCl4 with or without pretreatment with vitamin E (atocopherol). METHODS: Monocyte chemotactic protein-1 expression was analyzed by northern blotting and in situ hybridization and monocyte infiltration was determined by ED-1 immunostaining. The results were quantitated by computerized image analysis. Expression of MCP-1 mRNA was significantly increased as early as 12 hours following injury, and progressively increased thereafter. In contrast, a significant increase in the number of ED-1 positive cells, an index of monocyte infiltration, was observed only 24 and 48 hours after injury. RESULTS: Vitamin E markedly reduced MCP-1 expression at the mRNA and protein levels, and caused a significant reduction in the number of monocyte/macrophages, indicating a role for oxidative stress in the induction of MCP-1 expression in vivo. Accordingly, in cultured hepatic stellate cells, different oxidative stress-related molecules increased MCP-1 mRNA. CONCLUSIONS: These data suggest the existence of a direct relationship between MCP-1 expression and monocyte infiltration after acute liver injury, and that preventing the generation of oxidative stress-related molecules results in decreased expression and release of this chemokine.
AB - BACKGROUND: Increased expression of monocyte chemotactic protein-1 (MCP-1) has been indicated as a mechanism underlying leukocyte recruitment after liver injury. In this study we examined the temporal relationship between MCP-1 expression and the appearance of monocyte infiltration during acute liver injury. In addition, we tested the effects of vitamin E, a well known antioxidant, on these parameters. Rats were intoxicated with a single intragastric administration of CCl4 with or without pretreatment with vitamin E (atocopherol). METHODS: Monocyte chemotactic protein-1 expression was analyzed by northern blotting and in situ hybridization and monocyte infiltration was determined by ED-1 immunostaining. The results were quantitated by computerized image analysis. Expression of MCP-1 mRNA was significantly increased as early as 12 hours following injury, and progressively increased thereafter. In contrast, a significant increase in the number of ED-1 positive cells, an index of monocyte infiltration, was observed only 24 and 48 hours after injury. RESULTS: Vitamin E markedly reduced MCP-1 expression at the mRNA and protein levels, and caused a significant reduction in the number of monocyte/macrophages, indicating a role for oxidative stress in the induction of MCP-1 expression in vivo. Accordingly, in cultured hepatic stellate cells, different oxidative stress-related molecules increased MCP-1 mRNA. CONCLUSIONS: These data suggest the existence of a direct relationship between MCP-1 expression and monocyte infiltration after acute liver injury, and that preventing the generation of oxidative stress-related molecules results in decreased expression and release of this chemokine.
M3 - SCORING: Zeitschriftenaufsatz
VL - 47
SP - 66
EP - 75
JO - J INVEST MED
JF - J INVEST MED
SN - 1081-5589
IS - 1
M1 - 1
ER -