Abstract |
Atopic dermatitis (AD) is an inflammatory skin disease with intense pruritus, and chronic skin colonization by Staphylococcus aureus. To understand the inflammatory status in AD, we investigated the inflammasome complex, that activates ASC (Apoptosis-associated speck-like protein containing a CARD), caspase-1 and GSDMD (gasdermin-D), and production of IL-1β and IL-18. We aimed to evaluate the expression of the inflammasome pathway in the skin of adults with AD. Thirty patients with moderate to severe AD and 20 healthy controls were enrolled in the study. We performed the analysis of the inflammasome components NLRP1, NLRP3, AIM-2, IL-1β, IL-18, Caspase-1, ASC, GSDMD, and CD68 expression (macrophage marker) by immunohistochemistry and immunofluorescence. The main findings included increased expression of NLRP3, NLRP1 and AIM-2 at dermal level of severe AD; augmented IL-18 and IL-1β expression at epidermis of moderate and severe patients, and in the dermis of severe AD; augmented expression of ASC, caspase-1 and GSDMD in both epidermis and dermis of moderate and severe AD. We detected positive correlation between caspase-1, GSDMD and IL-1β (epidermis) and caspase-1 (dermis) and AD severity; NLRP3, AIM-2 and IL-1β, and NLRP3 with IL-18 in the epidermis; ASC, GSDMD and IL-1β, and NLRP3, AIM-2, caspase-1, and IL-18 in the dermis. We also evidenced the presence of CD68 |
MeSH term(s) |
Humans ; Inflammasomes/metabolism ; Inflammasomes/immunology ; CARD Signaling Adaptor Proteins/metabolism ; Dermatitis, Atopic/immunology ; Dermatitis, Atopic/metabolism ; Dermatitis, Atopic/pathology ; Macrophages/metabolism ; Macrophages/immunology ; Interleukin-1beta/metabolism ; Male ; Female ; Intracellular Signaling Peptides and Proteins/metabolism ; Phosphate-Binding Proteins/metabolism ; Adult ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; Interleukin-18/metabolism ; Caspase 1/metabolism ; Skin/pathology ; Skin/immunology ; Skin/metabolism ; Severity of Illness Index ; Middle Aged ; Antigens, Differentiation, Myelomonocytic/metabolism ; Young Adult ; Apoptosis Regulatory Proteins/metabolism ; Antigens, CD/metabolism ; NLR Proteins/metabolism ; Case-Control Studies ; Epidermis/immunology ; Epidermis/metabolism ; Epidermis/pathology ; Gasdermins ; CD68 Molecule ; DNA-Binding Proteins |
Chemical Substances |
Inflammasomes ; CARD Signaling Adaptor Proteins ; Interleukin-1beta ; Intracellular Signaling Peptides and Proteins ; Phosphate-Binding Proteins ; PYCARD protein, human ; NLR Family, Pyrin Domain-Containing 3 Protein ; IL1B protein, human ; Interleukin-18 ; GSDMD protein, human ; NLRP3 protein, human ; Caspase 1 (EC 3.4.22.36) ; NLRP1 protein, human ; AIM2 protein, human ; Antigens, Differentiation, Myelomonocytic ; Apoptosis Regulatory Proteins ; Antigens, CD ; IL18 protein, human ; CD68 antigen, human ; NLR Proteins ; Gasdermins ; CD68 Molecule ; DNA-Binding Proteins |
Language |
English |
Publishing date |
2024-05-11 |
Publishing country |
Germany |
Document type |
Journal Article ; Letter |
ZDB-ID |
130131-7 |
ISSN |
1432-069X ; 0340-3696 |
ISSN (online) |
1432-069X |
ISSN |
0340-3696 |
DOI |
10.1007/s00403-024-02899-0 |
Database |
MEDical Literature Analysis and Retrieval System OnLINE |