Translocation of the novel cytokine HMGB1 to the cytoplasm and extracellular space coincides with the peak of clinical activity in experimentally UV-induced lesions of cutaneous lupus erythematosus.
HMGB1 is a pro-inflammatory cytokine that together with TNF-alpha and IL-1beta is involved in the pathogenesis of spontaneously occurring skin lesions in lupus erythematosus. The purpose of the present study was to explore the sequence of events in HMGB1, TNF-alpha and IL-1beta expression under development and resolution of experimentally induced CLE lesions. The study involved investigation of 38 serial skin biopsies acquired from photoprovoked skin lesions of nine CLE patients, using immunohistochemical staining of tissue sections. In biopsies from the clinically most active phase of skin involvement extracellular, secreted HMGB1 and increased cytoplasmic HMGB1 were found, as compared with the late and fading lesions or non-lesional skin. Besides HMGB1, increased expression of TNF-alpha and IL-1beta was observed in dermal infiltrates of the induced CLE lesions. These cytokines were however not upregulated in all lesions, and increased expression of IL-1beta was seen predominantly in late biopsies.In conclusion, extracellular and cytoplasmic HMGB1 coincides with the clinically most active phase of photoinduced lesions of cutaneous lupus, and suggests that HMGB1 is an important factor in the inflammatory autoimmune process of CLE. HMGB1 can induce expression of TNF-alpha and IL-1beta, and formation of a pro-inflammatory loop between HMGB1, TNF-alpha, and IL-1beta may be responsible for the prolonged and sustained inflammation in CLE.
Barkauskaite
V
V
Rheumatology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden. vilija.barkauskaite@ki.se
Ek
M
M
Popovic
K
K
Harris
H E
HE
Wahren-Herlenius
M
M
Nyberg
F
F
D016207:Cytokines / Q000235:genetics; D003593:Cytoplasm / Q000378:metabolism; D005110:Extracellular Space / Q000378:metabolism; D005786:Gene Expression Regulation; D024243:HMGB1 Protein / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000209:etiology; D008178:Lupus Erythematosus, Cutaneous / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D021381:Protein Transport; D012867:Skin / Q000473:pathology; D014466:Ultraviolet Rays / Q000009:adverse effects
D016207:Cytokines; D024243:HMGB1 Protein