In situ detection of inflammatory cytokines and apoptosis in pemphigus foliaceus patients.
BACKGROUND
Endemic pemphigus foliaceus, or fogo selvagem, is a chronic autoimmune disease characterized by the formation of intraepidermal blisters that reduce adhesion between keratinocytes. Endemic pemphigus foliaceus is associated with the presence of autoantibodies and high levels of cytokines involved in the inflammatory response.


OBJECTIVE
To evaluate the expression of the proinflammatory cytokines interleukin 1, interferon gamma, and tumor necrosis factor alpha; the proapoptotic inducers Fas and inducible nitric oxide synthase; and the apoptosis inhibitor Bcl-2; and to evaluate the presence of apoptosis.


METHODS
Skin biopsies from 13 patients with endemic pemphigus foliaceus and controls were evaluated by immunohistochemistry and apoptosis was determined by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay.


RESULTS
Proinflammatory cytokines were only detected in cells of the inflammatory exudate. Inducible nitric oxide synthase, Fas, and Bcl-2 were expressed by both epithelial and inflammatory cells. Epithelial apoptosis was observed in 12 cases (92.3%), and subepithelial apoptosis in 11 cases (85%).


CONCLUSIONS
This study suggests that apoptosis as well as the local production of proinflammatory cytokines are associated with endemic pemphigus foliaceus lesions. These results may contribute to the development of new therapeutic approaches to endemic pemphigus foliaceus.
Rodrigues
Denise Bertulucci Rocha
DB
Laboratory of Immunology, Universidade Federal do Triangulo Mineiro, 38025-180 Uberaba, Minas Gerais, Brazil.
Pereira
Sanivia Aparecida Lima
SA
dos Reis
Marlene Antônia
MA
Adad
Sheila Jorge
SJ
Caixeta
João Eduardo
JE
Chiba
Angélica Maeda
AM
Sousa
Richard Atila
RA
Rodrigues
Virmondes
V
D017209:Apoptosis; D015415:Biomarkers / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000378:metabolism*; D019353:Endemic Diseases; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007371:Interferon-gamma / Q000378:metabolism; D007375:Interleukin-1 / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010392:Pemphigus / Q000378:metabolism* / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012867:Skin / Q000378:metabolism / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism
D015415:Biomarkers; D016207:Cytokines; D007375:Interleukin-1; D019253:Proto-Oncogene Proteins c-bcl-2; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D007371:Interferon-gamma; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II