Journal
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
Volume 281, Issue 5, Pages L1095-L1105Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajplung.2001.281.5.L1095
Keywords
inflammation; apoptosis; macrophage; benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone
Categories
Funding
- NIAID NIH HHS [AI-41637] Funding Source: Medline
Ask authors/readers for more resources
Although apoptosis has been observed in macrophages during the course of infections, the mechanism of apoptosis in activated macrophages is not fully understood. This study shows that pan-caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (ZVAD) or t-butyloxycarbonyl-Asp-fluoromethylketone (Boc-D) caused the death of lipopolysaccharide (LPS)-activated macrophages and RAW 264.7 cells with apoptotic features. The apoptosis was also observed in lipoprotein-treated bacteria but not in CpG oligonucleotide- or flagellin-treated macrophages, indicating a difference of cellular responses downstream of different Toll-like receptors. Consistent with the induction of cell death by pan-caspase inhibitors, no activation of known caspases was detected in LPS-ZVAD-treated cells, suggesting an involvement of unknown proapoptotic caspases in the cell death. ZVAD inhibited the activation of extracellular signal-regulated kinase (ERK) and p38 but not of nuclear factor (NF)-kappaB induced by LPS, suggesting that the ZVAD-sensitive molecule lies upstream of the ERK and p38 pathways but downstream of the divergent site of NF-kappaB and mitogen-activated protein kinases. Our results demonstrate that apoptosis of macrophages induced by LPS+ZVAD is independent from the known proapoptotic caspases and suggest that activity of an unidentified ZVAD-sensitive molecule( s) is involved in the survival of LPS-activated macrophages.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available