The role of chemokines in the pathogenesis of scleroderma.
OBJECTIVE
The triad of pathologic changes that defines systemic sclerosis (scleroderma) includes immune system activation with autoimmunity; an obliterative, proliferative small vessel vasculopathy; and fibrosis. Available data suggest that several cytokines, including chemokines, contribute to the development of scleroderma complications. This review focuses on chemokines and their contribution to tissue fibrosis and pulmonary hypertension in scleroderma.


RESULTS
Proteins and mRNAs for monocyte chemoattractant protein-1; pulmonary and activation-regulated chemokine; macrophage inflammatory protein-1, regulated upon activation normal T cell expressed and secreted; interleukin-8; and transforming growth factor-beta have been found in increased amounts in blood or involved tissue from scleroderma patients. These factors are likely to contribute directly to tissue damage in scleroderma through several pathways, including stimulation of extracellular matrix production, induction of TGF-beta production and activation, and chemoattraction of T cells and nonspecific inflammatory cells into tissues.


CONCLUSIONS
Multiple chemokines are part of the pathologic network that causes tissue damage in scleroderma, and, as such, may provide therapeutic targets in scleroderma.
Baltimore Veterans Administration Medical Center, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. satamas@umaryland.edu
Sergei P
SP
Atamas
Barbara
B
White
D000818:Animals; D015415:Biomarkers / Q000032:analysis; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D018932:Chemokine CCL2 / Q000378:metabolism; D018946:Chemokine CCL5 / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism*; D019742:Chemokines, CC / Q000378:metabolism; D005260:Female; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D008297:Male; D012595:Scleroderma, Systemic / Q000209:etiology* / Q000473:pathology*; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D013601:T-Lymphocytes / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D015415:Biomarkers; D018932:Chemokine CCL2; D018946:Chemokine CCL5; D018925:Chemokines; D019742:Chemokines, CC; D016209:Interleukin-8; D016212:Transforming Growth Factor beta