LPS pretreatment reprograms macrophage LPS‐stimulated TNF and IL‐1 release without protein tyrosine kinase activation

Autor: West, Michael A., Bennett, Terriel, Seatter, Susan C., Clair, Laurel, Bellingham, Janet
Zdroj: Journal of Leukocyte Biology; January 1997, Vol. 61 Issue: 1 p88-95, 8p
Abstrakt: Pretreatment of macrophages with low‐dose endotoxin (LPSp) profoundly alters cytokine release in response to subsequent LPSaactivation. These qualitative and quantitative alterations in cytokine release have been termed macrophage reprogramming. Macrophage activation by LPS is thought to occur via a mechanism involving an early protein tyrosine kinase (PTK) phosphorylation step. PTK inhibition with genistein or herbimycin A blocks LPSa‐stimulated secretion of tumor necrosis factor (TNF) and interleukin‐1 (IL‐1). In this study we investigated whether a PTK pathway participates in LPSppretreatment reprogramming. We show that LPSp pretreatment inhibited TNF and augmented IL‐1 release in response to subsequent LPSastimulation. Blockade of PTK activation pathways during the interval when macrophages were exposed to LPSp prevented mitogen‐activated protein kinase phosphorylation, as well as LPSp‐stimulated release of TNF and IL‐1, but did not block LPSpreprogramming effects. We conclude that LPSppretreatment reprogramming of macrophage cytokine production does not require PTK activation. J. Leukoc. Biol. 61: 88–95; 1997.
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