INTRODUZIONE Human skin is a dynamic organ with intense metabolic activity, continuously releasing volatile organic compounds (VOCs) from the stratum corneum, skin glands and resident microbiota. Alterations in VOC profiles have been associated with inflammatory skin conditions, including psoriasis and chronic dermatoses, highlighting their potential as non-invasive biomarkers of disease activity and therapeutic response. Here, a novel analytical methodology is presented for the quantification of volatile and semi-volatile compounds in a cellular model mimicking inflammatory skin conditions. METODI An in vitro fibroblast model (NHDF) was exposed to LPS, Poly I:C, and TNF-α to recapitulate key features of cutaneous inflammation. After 6 hours, 0.8 mL of cell supernatants were transferred into 20 mL headspace vials and stored at −80°C. Volatile metabolites were extracted by headspace SPME and analyzed using GC×GC-TOFMS. An internal standard fiber preloading strategy ensured analytical reliability across three biological replicates. The same platform was applied to serum samples (0.5 mL) from psoriatic patients and healthy controls, derivatized to monitor secondary metabolites, aiming to bridge in vitro inflammatory signatures with circulating VOC profiles. RISULTATI The combined volatile profile revealed more than 1,900 distinct chemical features; approximately 500 were retained after removal of control and blank signals. Multivariate analysis identified treatment-specific patterns, with separation between stimulated and non-stimulated groups, suggesting stimulus-associated differences in the fibroblast volatilome, though chemical identities remain to be confirmed. CONCLUSIONI This study establishes a robust analytical framework for characterizing the skin cell volatilome under inflammatory conditions. Translational extension to patient serum will enable comparison between in vitro signatures and circulating biomarkers in psoriatic individuals. Integrating immunometabolic screening with disease-specific VOC profiles may support novel biomarker identification and targeted therapeutic strategies for refractory inflammatory skin disorders.
SKIN CELL VOLATILOME PROFILING UNDER INFLAMMATORY CONDITIONS: BRIDGING IN VITRO MODELS AND CLINICAL BIOMARKERS
A. Marcuzzi
;E. Rimondi;E. Melloni;F. A. Franchina;R. Di Stefano;M. De Poli;E. Barbi;P. Secchiero
2026
Abstract
INTRODUZIONE Human skin is a dynamic organ with intense metabolic activity, continuously releasing volatile organic compounds (VOCs) from the stratum corneum, skin glands and resident microbiota. Alterations in VOC profiles have been associated with inflammatory skin conditions, including psoriasis and chronic dermatoses, highlighting their potential as non-invasive biomarkers of disease activity and therapeutic response. Here, a novel analytical methodology is presented for the quantification of volatile and semi-volatile compounds in a cellular model mimicking inflammatory skin conditions. METODI An in vitro fibroblast model (NHDF) was exposed to LPS, Poly I:C, and TNF-α to recapitulate key features of cutaneous inflammation. After 6 hours, 0.8 mL of cell supernatants were transferred into 20 mL headspace vials and stored at −80°C. Volatile metabolites were extracted by headspace SPME and analyzed using GC×GC-TOFMS. An internal standard fiber preloading strategy ensured analytical reliability across three biological replicates. The same platform was applied to serum samples (0.5 mL) from psoriatic patients and healthy controls, derivatized to monitor secondary metabolites, aiming to bridge in vitro inflammatory signatures with circulating VOC profiles. RISULTATI The combined volatile profile revealed more than 1,900 distinct chemical features; approximately 500 were retained after removal of control and blank signals. Multivariate analysis identified treatment-specific patterns, with separation between stimulated and non-stimulated groups, suggesting stimulus-associated differences in the fibroblast volatilome, though chemical identities remain to be confirmed. CONCLUSIONI This study establishes a robust analytical framework for characterizing the skin cell volatilome under inflammatory conditions. Translational extension to patient serum will enable comparison between in vitro signatures and circulating biomarkers in psoriatic individuals. Integrating immunometabolic screening with disease-specific VOC profiles may support novel biomarker identification and targeted therapeutic strategies for refractory inflammatory skin disorders.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
