Loading…
Histamine H3 Receptor Signaling Regulates the NLRP3 Inflammasome Activation in C2C12 Myocyte During Myogenic Differentiation
NLRP3 inflammasome has been implicated in impaired post-injury muscle healing and in muscle atrophy. Histamine receptors play an important role in inflammation, but the role of histamine H 3 receptor (H 3 R) in myocyte regeneration and in the regulation of NLRP3 inflammasome is not known. We studied...
Saved in:
Published in: | Frontiers in pharmacology 2021-05, Vol.12, p.599393-599393 |
---|---|
Main Authors: | , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
Summary: | NLRP3 inflammasome has been implicated in impaired post-injury muscle healing and in muscle atrophy. Histamine receptors play an important role in inflammation, but the role of histamine H
3
receptor (H
3
R) in myocyte regeneration and in the regulation of NLRP3 inflammasome is not known. We studied the effects of H
3
R signaling on C2C12 myocyte viability, apoptosis, and tumor necrosis factor alpha (TNFα)-induced NLRP3 inflammasome activation during striated myogenic differentiation at three time points (days 0, 3, and 6). Expression of
Nlrp3
, interleukin-1β (IL-1β), and myogenesis markers were determined. TNFα reduced overall viability of C2C12 cells, and exposure to TNFα induced apoptosis of cells at D6. Activation of H
3
R had no effect on viability or apoptosis, whereas inhibition of H
3
R increased TNFα-induced apoptosis. Stimulation of C2C12 cells with TNFα increased
Nlrp3
mRNA expression at D3 and D6. Moreover, TNFα reduced the expression of myogenesis markers MyoD1, Myogenin, and Myosin-2 at D3 and D6. H
3
R attenuated TNFα-induced expression of
Nlrp3
and further inhibited the myogenesis marker expression; while H
3
R -blockage enhanced the proinflammatory effects of TNFα and increased the myogenesis marker expression. TNFα-induced secretion of mature IL-1β was dependent on the activation of the NLRP3 inflammasome, as shown by the reduced secretion of mature IL-1β upon treatment of the cells with the small molecule inhibitor of the NLRP3 inflammasome (MCC950). The activation of H
3
R reduced TNFα-induced IL-1β secretion, while the H
3
R blockage had an opposite effect. In conclusion, the modulation of H
3
R activity regulates the effects of TNFα on C2C12 myocyte differentiation and TNFα-induced activation of NLRP3 inflammasome. Thus, H
3
R signaling may represent a novel target for limiting postinjury muscle inflammation and muscle atrophy. |
---|---|
ISSN: | 1663-9812 1663-9812 |
DOI: | 10.3389/fphar.2021.599393 |