Dear Editor, Systemic sclerosis (SSc) is a connective tissue disease characterized by vasculopathy, excessive accumulation of extracellular matrix (ECM), and Wbrosis of the skin and internal organs [1]. Although the precise pathogenesis of SSc is still unknown, it is generally accepted that the initial event in the development of SSc is the damage and subsequent activation of endothelial cells. This explanation was elucidated through the study of an animal model of SSc [2]. Evidence for endothelial cell damage and activation includes increased circulating levels of factor VIII/von Willebrand factor and increased levels of endothelin-1 (ET-1) [3]. A potent vasoconstrictive molecule ET-1 [4], Wrst characterized in 1988, has been found to induce the proliferation and activation of smooth muscle cells, Wbroblasts, and endothelial cells, thus inducing ECM production [5], and has also been shown to modulate the expression of adhesion molecules on Wbroblasts [6]. CD40 was originally described as B cell surface molecule, but CD40 is now known to be expressed by many other cell types as well, such as antigen presenting cells, endothelial cells, epithelial cells from diVerent organs, and Wbroblasts. Recently, moreover, the role of the CD40–CD40 ligand system in Wbroblast activation and lung Wbrosis has been reviewed and emphasized in the literature [7, 8]. Our aims were to determine CD40 expression on skin Wbroblasts from both normal controls and patients with SSc, and to investigate the role of ET-1 in CD40 expression. To do FACS analysis 1 £ 10 skin Wbroblasts from normal controls and SSc patients (provided by Korn JH, Boston University, Boston, MA, USA), and skin Wbroblasts (Detroit-551 from ATCC, Manassas, VA, USA) were plated on 6-well plates (Falcon, Franklin Lakes, NJ, USA) and incubated overnight. The normal skin Wbroblast cell strain was cultured for 72 h with recombinant human Interferon(IFN) (RD 236.8 § 35.1 vs. 120.4 § 15.4, P = 0.02 by t test), consistent with the result by Fukasawa et al. [9]. To ensure our experimental system working, we investigated ICAM-1 expression on skin Wbroblasts stimulated with 500 units of IFNand 100 nM of ET-1 for 72 h. As already known, these stimulators fairly induced ICAM1 expression on normal skin Wbroblast cell strain (Fig. 1b). To investigate the role of ET-1 on CD40 expression, we Dr. Korn deceased on March 6, 2005.