title: Supernatants from culture of type I collagen-stimulated PBMC from patients with cutaneous systemic sclerosis versus localized scleroderma demonstrate suppression of MMP-1 by fibroblasts.
abstract: Systemic sclerosis (SSc) is a chronic fibrosing disease characterized by vasculopathy, autoimmunity, and an accumulation of collagen in tissues. Numerous studies have shown that compared to healthy or diseased controls, the peripheral blood mononuclear cells (PBMC) from patients with SSc produce a variety of cytokines or proliferate when cultured with solubilized type I collagen (CI) or constituent α1(II) and α2(I) polypeptide chains. The purpose of this study was to determine whether PBMC isolated from patients with SSc and cultured in vitro with soluble CI elaborated soluble mediators that inhibit the production of collagenase (i.e., matrix metalloproteinase, MMP-1) by fibroblasts. Supernatants of CI-stimulated PBMC from juvenile and adult diffuse cutaneous (dc)SSc patients significantly reduced MMP-1 production by SSc dermal fibroblasts, while supernatants of CI-stimulated PBMC from patients with localized scleroderma (LS) did not. CI-stimulated PBMC culture supernatants from patients with dcSSc in contrast to patients with LS exhibited increased levels of platelet-derived growth factor (PDGF)-AA, PDGF-BB, TNF-α, IL-13, and EGF. Prolonged culture of SSc dermal fibroblasts with recombinant PDGF-BB or IL-13 inhibited the induction of MMP-1 in response to subsequent TNF-α stimulation. These data suggest that therapies aimed at reducing these cytokines may decrease collagen accumulation in SSc, preventing the development of chronic fibrosis.
authors.affiliation: Le Bonheur Children's Medical Center, Department of Pediatrics, Division of Clinical Immunology, University of Tennessee Health Science Center, 956 Court Avenue, Memphis, TN 38163, USA. mbrown67@uthsc.edu
authors.forename: Monica
authors.initials: M
authors.lastname: Brown
authors.forename: Arnold E
authors.initials: AE
authors.lastname: Postlethwaite
authors.forename: Linda K
authors.initials: LK
authors.lastname: Myers
authors.forename: Karen A
authors.initials: KA
authors.lastname: Hasty
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015551:Autoimmunity; D000077214:Becaplermin; D002478:Cells, Cultured / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D024042:Collagen Type I / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D018793:Interleukin-13 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology*; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism*; D008875:Middle Aged; D020574:Proto-Oncogene Proteins c-sis / Q000378:metabolism; D012594:Scleroderma, Localized / Q000097:blood* / Q000175:diagnosis; D012595:Scleroderma, Systemic / Q000097:blood* / Q000175:diagnosis; D012867:Skin / Q000473:pathology*; D012871:Skin Diseases / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D024042:Collagen Type I; D016207:Cytokines; D018793:Interleukin-13; D020574:Proto-Oncogene Proteins c-sis; D014409:Tumor Necrosis Factor-alpha; D000077214:Becaplermin; D003094:Collagen; D020781:Matrix Metalloproteinase 1