Epigenetic Studies Revealed a Ghost Proteome in PC1/3 KD Macrophages under Antitumoral Resistance Induced by IL-10

Our
previous investigation on macrophages has allowed us to show
that the inhibition of the enzyme proprotein convertase (PC1/3) controls
the activation of macrophages. We demonstrated that PC1/3 knockdown
(KD) in macrophages exhibits an increased secretion of proinflammatory
and antitumoral factors. In this biological context, we assessed the
presence of histone modifications and the presence and contribution
of a “ghost proteome” in these macrophages.
We identified a set of alternative proteins (AltProts) that have a
key role in the regulation of various signaling pathways. In this
study, to further investigate the underlying mechanisms involved in
the resistance of PC1/3-KD macrophages to anti-inflammatory stimuli,
we have conducted a proteomic system biology study to assess the epigenome
variation, focusing on histone modifications. Results from our study
have indicated the presence of significant variations in histone modifications
along with the identification of 28 AltProts, which can be correlated
with antitumoral resistance under IL-10 stimulation. These findings
highlight a key role of altered epigenome histone modifications in
driving resistance and indicate that like the reference proteins,
AltProts can have a major impact in the field of epigenetics and regulation
of gene expression, as shown in our results.