ABSTRACT
Introduction: Exosomes play a key role in cell communication and are involved in both pathological and physiological processes. Autophagy dysfunction and oxidative stress are linked to immune-mediated inflammatory diseases such as psoriasis. Stem cell-derived exosomes exhibit immunomodulatory and antioxidant efficacy. Methods: We aimed to investigate the impact of psoriasis serum-derived exosomes on inflammation, oxidative stress, and autophagy in keratinocytes. Additionally, we explored the therapeutic potential of adipose-derived stem cell (ADSC) exosomes against inflammation induced by psoriasis serum exosomes. To validate psoriasis patient serum-derived exosomes and ADSC exosomes, we used nanoparticle tracking analysis, Western blotting, flow cytometry, and immunofluorescence. qPCR was used to study changes in the gene expression of proinflammatory cytokines and oxidative stress markers in HaCaT cells treated with psoriasis serum-derived exosomes or ADSC exosomes. The effects of these exosomes on autophagy in HaCaT cells were evaluated by Western blotting and immunofluorescence. Result: The treatment of HaCaT cells with psoriasis serum-derived exosomes increased proinflammatory cytokine production and oxidative stress-related factor (Nox2 and Nox4) expression and decreased Nrf2 expression via P65/NF-κB and P38/MAPK activation. Compared with healthy control serum-derived exosomes, psoriasis serum-derived exosomes decreased ATG5, P62, Beclin1, and LC3 expression and autophagosome production in HaCaT cells. Conversely, ADSC exosomes suppressed proinflammatory cytokine and oxidative stress production, and restored autophagy in HaCaT cells treated with psoriasis serum-derived exosomes. Discussion: These findings suggest that ADSC exosomes exhibit a suppressive effect on psoriasis serum exosome-induced inflammation and oxidative stress by regulating autophagy in keratinocytes.
ABSTRACT
Introduction: Exosomes, pivotal in intercellular communication during skin disease pathogenesis, have garnered substantial attention. However, the impact of environmental pollutants, such as benzo[a]pyrene (BaP) and 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD), on exosome release amid inflammatory skin diseases remains unexplored. This study addresses this gap by examining the influence of BaP and TCDD on exosome function, specifically focusing on immune-related pathway alterations in normal recipient keratinocytes and peripheral blood mononuclear cells (PBMCs). Methods: HaCaT cells were treated with exosomes from BaP- or TCDD-treated keratinocytes. Proinflammatory cytokines and chemokines, including TNF-α, IL-1ß, IL-6, IL-8, CXCL1, and CXCL5, were assessed. The involvement of the p65NF-κB/p38MAPK/ERK signaling pathway in recipient keratinocytes was investigated. Aryl hydrocarbon receptor (AhR) silencing was employed to elucidate its role in mediating the proinflammatory response induced by exosomes from BaP- or TCDD-treated keratinocytes. Results and discussion: Treatment with exosomes from BaP- or TCDD-treated keratinocytes induced a significant increase in proinflammatory cytokines and chemokines in HaCaT cells. The upregulation implicated the p65NF-κB/p38MAPK/ERK signaling pathway. AhR silencing attenuated this response, suggesting a role for AhR in mediating this response. In PBMCs from healthy controls, exosomes from BaP-stimulated PBMCs of psoriatic patients led to increased expression of proinflammatory cytokines and modulation of Th1/Th17 cell distribution via AhR activation. These findings unveil a novel dimension in the interplay between environmental xenobiotic agents (BaP and TCDD) and exosomal functions. The study establishes their influence on psoriatic inflammatory responses, shedding light on the underlying mechanisms mediated through the AhR signaling pathway in recipient keratinocytes and PBMCs.