Lipidomics Profiling of Hidradenitis Suppurativa Skin Lesions Reveals Lipoxygenase Pathway Dysregulation and Accumulation of Proinflammatory Leukotriene B4.
J Invest Dermatol
; 140(12): 2421-2432.e10, 2020 12.
Article
in En
| MEDLINE
| ID: mdl-32387270
ABSTRACT
Hidradenitis suppurativa (HS) is a chronic, recurring inflammatory dermatosis characterized by abscesses, deep-seated nodules, sinus tracts, and fibrosis in skin lesions around hair follicles of the axillary, inguinal, and anogenital regions. Whereas the exact pathogenesis remains poorly defined, clear evidence suggests that HS is a multifactorial inflammatory disease characterized by innate and adaptive immune components. Bioactive lipids are important regulators of cutaneous homeostasis, inflammation, and resolution of inflammation. Alterations in the lipid mediator profile can lead to malfunction and cutaneous inflammation. We used targeted lipidomics to analyze selected omega-3 and omega-6 polyunsaturated fatty acids in skin of patients with HS and of healthy volunteers. Lesional HS skin displayed enrichment of 5-lipoxygenase (LO)âderived metabolites, especially leukotriene B4. In addition, 15-LOâderived metabolites were underrepresented in HS lesions. Changes in the lipid mediator profile were accompanied by transcriptomic dysregulation of the 5-LO and 15-LO pathways. Hyperactivation of the 5-LO pathway in lesional macrophages identified these cells as potential sources of leukotriene B4, which may cause neutrophil influx and activation. Furthermore, leukotriene B4-induced mediators and pathways were elevated in HS lesions, suggesting a contribution of this proinflammatory lipid meditator to the pathophysiology of HS.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Skin
/
Arachidonate 5-Lipoxygenase
/
Arachidonate 15-Lipoxygenase
/
Hidradenitis Suppurativa
/
Leukotriene B4
Type of study:
Observational_studies
Limits:
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
J Invest Dermatol
Year:
2020
Document type:
Article
Affiliation country: