Spontaneous cytokine gene expression by cultured skin fibroblasts of systemic sclerosis. Correlation with collagen synthesis.
OBJECTIVE
To investigate the spontaneous cytokine gene expression in fibroblasts from patients with diffuse cutaneous systemic sclerosis. Their pattern of expression was correlated with the production of collagen.


METHODS
Fibroblasts were obtained from skin biopsies of nine patients diagnosed with systemic sclerosis (mean 16 +/- 8.7 years of disease duration) and ten control individuals. The cytokine gene expression was detected by coupled reverse transcriptase polymerase chain reaction for interleukins 1 beta, 6, 8, tumour necrosis factor-alpha, and transforming growth factor beta. In addition, collagen synthesis was measured by [14C]-proline uptake in fibroblast cultures.


RESULTS
All fibroblast samples from patients expressed the interleukin-6 gene (p = 0.04 compared with controls). Eight of the nine patients expressed interleukin-8 (p = 0.02 compared with controls). Four of them expressed also transforming growth factor beta and two more weakly expressed the tumour necrosis factor-alpha gene. Only one patient showed transcription for the interleukin-1 beta gene. In accordance with such immune activation, collagen synthesis was higher in fibroblasts from patients with systemic sclerosis (p = 0.028) as compared with normal controls. Indeed, a positive correlation was found between the expression of IL-6 gene and collagen production (rs = 1).


CONCLUSIONS
The constitutive expression of IL-6 and IL-8 genes by fibroblasts may play an important role in the perpetuation of local immune dysregulation, thus leading to a permanent fibroblast activation in patients with systemic sclerosis.
Zurita-Salinas
C S
CS
Department of Immunology and Rheumatology, Instituto Nacional de la Nutrición Salvador Zubirán, Mexico City, Mexico.
Richaud-Patin
Y
Y
Krötzsch-Gómez
E
E
Llorente
L
L
Alcocer-Varela
J
J
Díaz-de-León
L
L
Palacios-Boix
A
A
D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis*; D016207:Cytokines / Q000235:genetics*; D004247:DNA / Q000032:analysis; D005260:Female; D005347:Fibroblasts; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D011392:Proline / Q000378:metabolism; D012595:Scleroderma, Systemic / Q000235:genetics* / Q000276:immunology
D016207:Cytokines; D003094:Collagen; D004247:DNA; D011392:Proline