What question did this study set out to answer?

To determine the cellular fate and functional impact of unprocessed pro-TNF-alpha when metalloprotease-mediated cleavage is inhibited in human monocytes.

November 1, 1997The Journal of Immunology

The fate of pro-TNF-alpha following inhibition of metalloprotease-dependent processing to soluble TNF-alpha in human monocytes

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Authors

KSKimberly A. SolomonUniversity of North Florida MCMaryanne CovingtonIncyte (United States)CDCarl P. DeciccoFlagship Pioneering (United States)

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Implication

In vitro study reveals rapid intracellular degradation of unprocessed pro-TNF-alpha in human monocytes following metalloprotease inhibition, highlighting alternative clearance pathways.

Key Points

To determine the cellular fate and functional impact of unprocessed pro-TNF-alpha when metalloprotease-mediated cleavage is inhibited in human monocytes.
Stimulated human monocytes with bacterial lipopolysaccharide in the presence or absence of hydroxamic acid-based metalloprotease inhibitors and brefeldin A.
Characterized protein processing and membrane expression using N-terminal sequencing, flow cytometry, L929 tumor cell cytotoxicity assays, and pulse-chase radiolabeling.
Metalloprotease inhibition blocked >95% of soluble 17-kDa TNF-alpha production and transiently increased functional cell-surface TNF-alpha, which enhanced L929 tumor target killing and gingival fibroblast prostaglandin production.
Surface accumulation did not quantitatively account for the unsecreted cytokine, with pulse-chase analysis demonstrating rapid degradation of unprocessed 26-kDa pro-TNF-alpha within monocytes.
Brefeldin A treatment indicated that proteolytic cleavage occurs at a post-endoplasmic reticulum site tightly coupled with transport to the cell surface.

Cite This Study

Solomon et al. (1997) studied this question.

synapsesocial.com/papers/6a6f3339f44fa9f079dc9cb9 https://doi.org/10.4049/jimmunol.159.9.4524

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Implication

In vitro study reveals rapid intracellular degradation of unprocessed pro-TNF-alpha in human monocytes following metalloprotease inhibition, highlighting alternative clearance pathways.

The fate of pro-TNF-alpha following inhibition of metalloprotease-dependent processing to soluble TNF-alpha in human monocytes

Discussion

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Implication

Key Points

Cite This Study

The fate of pro-TNF-alpha following inhibition of metalloprotease-dependent processing to soluble TNF-alpha in human monocytes

Discussion

Member takes

Implication

Key Points

Cite This Study

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