ABSTRACT
Staphylococcus aureus may perform an crucial function in atopic dermatitis (AD), via the secretion of superantigens, including staphylococcal enterotoxins (SE) A or B, and toxic shock syndrome toxin-1 (TSST-1). Dysregulated cytokine production by keratinocytes (KCs) upon exposure to staphylococcal superantigens (SsAgs) may be principally involved in the pathophysiology of AD. We hypothesized that lesional KCs from AD may react differently to SsAgs compared to nonlesional skin or normal skin from nonatopics. We conducted a comparison of HLA-DR or CD1a expression in lesional skin as opposed to that in nonlesional or normal skin by immunohistochemistry (IHC). We also compared, using ELISA, the levels of IL-1alpha, IL-1beta, and TNF-alpha secreted by cultured KCs from lesional, nonlesional, and normal skin, after the addition of SEA, SEB and TSST-1. IHC revealed that both HLA-DR and CD1a expression increased significantly in the epidermis of lesional skin versus nonlesional or normal skin in quite a similar manner. IL-1alpha, IL-1beta, and TNF-alpha secretion was also significantly elevated in the cultured KCs from lesional skin after the addition of SsAgs. Our results indicated that KCs from lesional skin appear to react differently to SsAgs and increased proinflammatory cytokine production in response to SsAgs may contribute to the pathogenesis of AD.
Subject(s)
Male , Humans , Adult , Tumor Necrosis Factor-alpha/biosynthesis , Superantigens/administration & dosage , Staphylococcus aureus/immunology , Keratinocytes/immunology , Interleukin-1/biosynthesis , Inflammation Mediators/metabolism , HLA-DR Antigens/metabolism , Enterotoxins/administration & dosage , Dermatitis, Atopic/etiology , DNA, Complementary/genetics , Case-Control Studies , Base Sequence , Bacterial Toxins/administration & dosage , Antigens, CD1/metabolismABSTRACT
Los superantígenos son proteínas bacterianas y virales con capacidad de estimular gran número de células T; se conjugan con MHC-II de la célula presentadora de antígeno de manera diferente a los antígenos comunes, uniéndose a la subfamilia del V beta del TCR del linfocito T, siendo importante en el desencadenamiento de enfermedades sistémicas leves, intoxicación alimentaria o enfermedades severas como el sindrome del shock tóxico y síndrome de Kawasaki; algunas enfermedades cutáneas autoinmunes como la artritis reumatoidea y la encefalomielitis alérgica experimental; deleción y apoptosis por superantígenos como el del Mitógeno de Mycoplasma artritidis (MAM), superantígenos virales como el del HIV-1; por ello la utilización de inmunoglobulinas endovenosas para controlar dichos cuadros, o la modificación de toxinas (superantígenas) constituyen avances importantes en el manejo de estas enfermedades autoinmunes