BMAL1 regulates Propionibacterium acnes-induced skin inflammation via REV-ERBα in mice

Apr 13, 2022International journal of biological sciences

BMAL1 controls skin inflammation caused by acne bacteria through REV-ERBα in mice

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Abstract

Over 80% of adolescents are affected by acne vulgaris, highlighting its prevalence.

Inflammation plays a central role in the development of acne.
Specific central clock genes and their target genes are down-regulated in acne-associated inflammation in mice.
Deletion or disruption of the central clock gene exacerbates inflammation induced by acne-related bacteria.
Inflammation regulation is linked to the NF-κB/NLRP3 signaling pathway, which is influenced by the central clock gene.
Disruption of the central clock gene may be a pathological factor in acne-associated inflammation.

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Acne vulgaris is a common skin disease, affecting over 80% of adolescents. Inflammation is known to play a central role in acne development. Here, we aimed to investigate the role of the central clock genein acne-associated inflammation in mice. To this end, mice were injected intradermally with() to induce acne-associated skin inflammation. We found thatand its target genesandwere down-regulated in the skin of-treated mice, suggesting a role ofin the condition of acne. Supporting this,-deleted or jet-lagged mice showed exacerbated-induced inflammation in the skin. Regulation of-induced inflammation bywas further confirmed in RAW264.7 cells and primary mouse keratinocytes. Transcriptomic and protein expression analyses suggested thatregulated-induced inflammation via the NF-κB/NLRP3 axis, which is known to be repressed by REV-ERBα (a direct target of BMAL1). Moreover, loss ofin mice exacerbated-induced inflammation. In addition,silencing attenuated the inhibitory effects ofon-induced inflammation.knockdown failed to modulate-induced inflammation in-silenced cells. It was thus proposed thatrestrained-induced skin inflammation via its target REV-ERBα, which acts on the NF-κB/NLRP3 axis to repress inflammation. In conclusion,disruption is identified as a potential pathological factor of acne-associated inflammation. The findings increase our understanding of the crosstalk between skin clock and acne and suggest targeting circadian rhythms as a promising approach for management of acne. Bmal1Propionibacterium acnes P. acnes Bmal1Rev-erbα, Dbp, Per1Cry2P. acnes Bmal1Bmal1P. acnes P. acnes Bmal1Bmal1P. acnes Rev-erbα P. acnes Rev-erbα Bmal1P. acnes Bmal1P. acnes Rev-erbα Bmal1P. acnes Bmal1

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BMAL1 regulates Propionibacterium acnes-induced skin inflammation via REV-ERBα in mice

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