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Skin-Derived Precursors-Derived Exosomes Alleviated Acne Inflammation via TLR2/MyD88/NF-κB Signaling Pathway: In Vitro and In Vivo Studies
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DOI：10.1096/fj.202501944R.png)
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Abstract
En 中文
Skin-derived precursors (SKPs) isolated from the dermis are poorly immunogenic and capable of modulating the allogeneic immune responses. Previous studies implied mouse SKPs-derived exosomes (mSKPs-exo) might possess immunomodulatory functions. In the present study we collected mSKPs-exo using ultracentrifugation method and characterized them. We then explored mSKPs-exo's impact on acne inflammation with Cutibacterium acnes (C. acnes)-challenged murine monocyte-macrophages RAW264.7 and Sprague Dawley (SD) rats auricular acne model. The in vitro studies demonstrated mSKPs-exo reduced nitric oxide, TNF-alpha, and IL-6 concentration in C. acnes-challenged RAW264.7 cells supernatant. mSKPs-exo also ameliorated NF-kappa B p65 nuclear translocation and CD86 and iNOS antigens expression in C. acnes-challenged RAW264.7 cells. The RT-PCR and Western blots revealed mSKPs-exo alleviated inflammation by regulating key genes (TLR2, TNF-alpha, MyD88, and IL-6) and proteins (TLR2, MyD88, I kappa Ba, and NF-kappa Bp65) in the TLR2/MyD88/NF-kappa B pathway. The anti-inflammatory effects could be synergistically enhanced by I kappa B/IKK inhibitor. The in vivo studies validated mSKPs-exo's efficacy on acne inflammation and TLR2/MyD88/NF-kappa B pathway. Topical dermal injection of mSKPs-exo alleviated auricular inflammatory manifestations in SD rats. Immunohistochemistry and Western blot results indicated mSKPs-exo reduced the expression of TLR2, MyD88, MMP3, p-p38 MAPK, and NF-kappa B p65. The effect was comparable with topical adapalene gel application. The current study initiated mSKPs-exo research and provided theoretical support and experimental data for their potential application in inflammation regulation, acne treatment, and novel therapeutic targets identification.
Keywords:
acne vulgaris
exosomes
inflammation
skin-derived precursors
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4.2
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4.9W
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