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@ARTICLE{CardonaGloria:278419,
author = {Y. Cardona Gloria and A. N. R. Weber$^*$},
title = {{I}nflammasome {A}ctivation in {H}uman {M}acrophages:
{IL}-1β {C}leavage {D}etection by {F}ully {A}utomated
{C}apillary-{B}ased {I}mmunoassay.},
journal = {Methods in molecular biology},
volume = {2696},
issn = {1064-3745},
address = {[Heidelberg]},
publisher = {[Springer]},
reportid = {DKFZ-2023-01653},
isbn = {978-1-0716-3349-6 (print)},
pages = {239-256},
year = {2023},
note = {Second Edition},
abstract = {Interleukin (IL)-1β is a key mediator of inflammation and
activates via pattern recognition receptors (PRR) of the
inflammasome family by proteolytic maturation. Proteolysis
is driven by proteases such as caspase-1 (also known as IL-1
converting enzyme, ICE) and converts the intact pro-IL-1β
~31 kDa pro-peptide into a mature, ~17 kDa form that can
exit cells through nanomolecular pores or via microvesicles.
Whereas pro-IL-1β fails to trigger IL-1 receptor (IL-1R)
activation, mature IL-1β, upon release from the cell,
triggers pleiotropic downstream effects, establishing an
inflammatory state. Hence, being able to detect IL-1β
conversion is physiologically relevant for measuring
inflammation, but it cannot be easily accomplished by
conventional ELISA or flow cytometry as most commercially
available antibodies do not discriminate mature and
pro-form. Furthermore, unlike for other cytokines, the mere
induction and translation of IL1B mRNA cannot serve as a
proxy of inflammasome PRR activation. Rather the cleavage of
IL-1β needs to be verified. Hence, conventional
immunoblotting has emerged as the gold standard for
demonstrating inflammasome activation as the difference in
molecular weight between pro- and mature form can easily be
detected. However, conventional immunoblotting suffers from
poor standardization, quantification, and reproducibility,
may require sample concentration, and is also not suitable
for medium to high throughput. Some of these shortcomings
are prohibitive for analysis of human primary samples but
can be overcome by fully automated capillary-based
immunoassay as we outline here. We here provide a practical
guide to quantify pro- vs mature IL-1β directly from
unconcentrated supernatants of human monocyte-derived
macrophages. The assay may be useful for more standardized
and medium-throughput analysis in these cells or other
biospecimen.},
keywords = {Humans / Inflammasomes / NLR Family, Pyrin
Domain-Containing 3 Protein / Reproducibility of Results /
Cells, Cultured / Macrophages / Interleukin-1beta /
Immunoblotting / Inflammation / Caspase 1 / Automated
capillary-based immunoassay (Other) / Caspase-1 (Other) /
Human macrophages (Other) / IL-1β (Other) / Inflammasome
(Other) / NLRP3 (Other) / Inflammasomes (NLM Chemicals) /
NLR Family, Pyrin Domain-Containing 3 Protein (NLM
Chemicals) / Interleukin-1beta (NLM Chemicals) / Caspase 1
(NLM Chemicals)},
cin = {TU01},
ddc = {570},
cid = {I:(DE-He78)TU01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)3 / PUB:(DE-HGF)16},
pubmed = {pmid:37578727},
doi = {DOI:10.1007/978-1-0716-3350-2_16},
url = {https://inrepo02.dkfz.de/record/278419},
}