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• W2072534789 abstract "BACKGROUND: Phosphorylation of extracellular signal‐regulated kinase (ERK) enhances various inflammatory responses in immune cells. It is unknown whether dysfunction of immune cells during malnutrition is attributed to derangement of ERK activation. METHODS: Male Institute of Cancer Research (ICR) mice received chow (146 g/kg per day, ad libitum or 36.5 g/kg per day, diet‐restricted) for 7 days. Mice (n = 55) were given 6.5 mg/kg of an ERK inhibitor (PD98059) or vehicle intraperitoneally (IP), at 2 hours before cecal ligation and puncture (CLP). Survival was observed up to 60 hours. Detection of phosphorylated ERK (pERK) in the peritoneal exudative cells (PECs) was done as follows. In a separate study, PECs were harvested by peritoneal lavage 2 hours after an IP injection of 1% glycogen. PECs were incubated with or without 100 nmol/L N‐formyl‐methionyl‐leucyl‐phenylalanine (fMLP) for 1 minute. PEC ERK activation was detected with Western blot analysis (n = 38), by densitometric quantification, and with a laser scanning cytometer (LSC; n = 13). Subpopulations of PECs were determined by Wright‐Giemsa staining. Unstimulated pERK expression was normalized to 100% for Western blot analysis. RESULTS: Diet restriction reduced survival after CLP compared with the ad libitum mice. ERK inhibition showed no effect on survival in diet‐restricted mice but reduced survival in ad libitum mice. There were no differences in subpopulations of PECs 2 hours after glycogen injection between the groups. Western blot analysis revealed that fMLP stimulation significantly increased the phosphorylation of ERK1/2 in PECs from the ad libitum group (ERK1, 199 +/‐ 41%; ERK2, 211 +/‐ 49%; p <.03) but not in those from diet‐restricted mice (ERK1, 98 +/‐ 10%; ERK2, 91 +/‐ 9%). Mean fluorescence intensity (MFI) of pERK in PECs obtained by LSC was significantly elevated after fMLP in the ad libitum group (from 19.4 +/‐ 1.5 MFI to 22.4 +/‐ 1.2 MFI; p <.05) but did not change in the diet‐restricted group (from 19.4 +/‐ 1.8 MFI to 19.1 +/‐ 1.5 MFI). CONCLUSIONS: ERK activation is essential for survival in this murine sepsis model. Impaired ERK activation of PECs may, at least in part, impair host defense during malnutrition." @default.
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• W2072534789 date "2002-09-01" @default.
• W2072534789 modified "2023-10-16" @default.
• W2072534789 title "Diet restriction impairs extracellular signal-regulated kinase activation of peritoneal exudative cells after N-formyl-methionyl-leucyl-phenylalanine stimulation in a murine peritonitis model" @default.
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• W2072534789 doi "https://doi.org/10.1177/0148607102026005259" @default.
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