Butyrate inhibits Staphylococcus aureus-aggravated dermal IL-33 expression and skin inflammation through histone deacetylase inhibition

Chia-Hui Luo; Alan Chuan-Ying Lai; Ya-Jen Chang

doi:10.3389/fimmu.2023.1114699

Butyrate inhibits Staphylococcus aureus-aggravated dermal IL-33 expression and skin inflammation through histone deacetylase inhibition

Front Immunol. 2023 May 16:14:1114699. doi: 10.3389/fimmu.2023.1114699. eCollection 2023.

Authors

Chia-Hui Luo^{1

2}, Alan Chuan-Ying Lai^{1

3}, Ya-Jen Chang^{1

4}

Affiliations

¹ Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
² Taiwan International Graduate Program in Molecular Medicine, National Yang Ming Chiao Tung University and Academia Sinica, Taipei, Taiwan.
³ Department of Pharmaceutical Sciences, School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan.
⁴ Institute of Translational Medicine and New Drug Development, China Medical University, Taichung, Taiwan.

Abstract

Atopic dermatitis (AD) is an inflammatory skin disease caused by the disruption of skin barrier, and is dominated by the type 2 immune responses. Patients with AD have a high risk of developing Staphylococcus aureus infection. Interleukin-33 (IL-33), an alarmin, has been implicated in the pathophysiology of AD development. Butyrate, a short chain fatty acid known to be produced from the fermentation of glycerol by the commensal skin bacterium, Staphylococcus epidermidis, has been reported to possess antimicrobial and anti-inflammatory properties that suppress inflammatory dermatoses. However, little is known about the effects of butyrate on dermal IL-33 expression and associated immune response in S. aureus-aggravated skin inflammation in the context of AD. To decipher the underlying mechanism, we established an AD-like mouse model with epidermal barrier disruption by delipidizing the dorsal skin to induce AD-like pathophysiology, followed by the epicutaneous application of S. aureus and butyrate. We discovered that S. aureus infection exacerbated IL-33 release from keratinocytes and aggravated dermal leukocyte infiltration and IL-13 expression. Moreover, we showed that butyrate could attenuate S. aureus-aggravated skin inflammation with decreased IL-33, IL-13, and leukocyte infiltration in the skin. Mechanistically, we demonstrated that butyrate suppressed IL-33 expression and ameliorated skin inflammation through histone deacetylase 3 (HDAC3) inhibition. Overall, our findings revealed the potential positive effect of butyrate in controlling inflammatory skin conditions in AD aggravated by S. aureus infection.

Keywords: S. aureus; S. epidermidis; atopic dermatitis; butyrate; histone deacetylase; interleukin 33; keratinocytes.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Butyrates / pharmacology
Butyrates / therapeutic use
Dermatitis, Atopic*
Inflammation / complications
Inflammation / drug therapy
Interleukin-13
Interleukin-33
Mice
Staphylococcal Infections* / drug therapy
Staphylococcal Infections* / microbiology
Staphylococcus aureus

Substances

Interleukin-33
Butyrates
Interleukin-13

Grants and funding

This work was supported by the National Health Research Institutes [NHRI-EX110-10836SI], Ministry of Science and Technology [104-2320-B-001-022; 111-2320-B-001-025-MY3] and by the Academia Sinica [AS-IA-110-L04 and AS-GC-110-05 to Y-JC] in Taiwan.