Increased expression of the novel proinflammatory cytokine high mobility group box chromosomal protein 1 in skin lesions of patients with lupus erythematosus.
OBJECTIVE
To investigate the role of the novel cytokine high mobility group box chromosomal protein 1 (HMGB-1) in the pathogenesis of cutaneous lupus erythematosus (CLE).


METHODS
Punch biopsy specimens of lesional and unaffected skin from 10 patients with CLE and 3 healthy control subjects were investigated. Immunohistochemical staining for HMGB-1, tumor necrosis factor alpha (TNFalpha), and interleukin-1beta (IL-1beta) was performed on consecutive sections. Analysis of single-nucleotide polymorphisms of -308 TNF was performed on DNA extracted from peripheral blood mononuclear cells.


RESULTS
An altered expression of HMGB-1 was observed both in the epidermis and in the dermal infiltrates of lesional skin. Expression of HMGB-1 in the epidermis and dermis was increased (P < 0.01 and P < 0.001, respectively, versus unaffected skin), and translocation to the cytoplasm as well as the extracellular presence of secreted HMGB-1 were found. Increased levels of TNFalpha and IL-1beta were also observed in the dermal infiltrates of lesional skin (P < 0.01 and P < 0.05, respectively, versus unaffected skin). The carrier frequency of the -308A TNF polymorphism was 80% in patients with subacute CLE, but this was not related to higher expression of TNFalpha in biopsy specimens from the CLE group.


CONCLUSIONS
The high amount of extracellular HMGB-1 observed in skin lesions indicates that HMGB-1 is involved in the inflammatory process of CLE. TNFalpha and IL-1beta may form a proinflammatory loop with HMGB-1, since they can induce the release of each other. The extracellular HMGB-1 observed by immunostaining of the epidermis indicates that keratinocytes may be an as yet unrecognized source of secreted HMGB-1, underscoring the role of the target organ in the rheumatoid autoimmune inflammatory process.
Popovic
Karin
K
Department of Dermatology, Karolinska Institutet at Danderyd Hospital, S-182 88 Stockholm, Sweden. karin.popovic@cmm.ki.se
Ek
Monica
M
Espinosa
Alexander
A
Padyukov
Leonid
L
Harris
Helena Erlandsson
HE
Wahren-Herlenius
Marie
M
Nyberg
Filippa
F
D000328:Adult; D000368:Aged; D004247:DNA / Q000235:genetics; D005260:Female; D024243:HMGB1 Protein / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000378:metabolism; D015603:Keratinocytes / Q000378:metabolism / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000737:chemistry / Q000473:pathology; D008178:Lupus Erythematosus, Cutaneous / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012867:Skin / Q000378:metabolism* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D024243:HMGB1 Protein; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D004247:DNA