Affiliations: UMR 7561 CNRS-Nancy-Université, Laboratoire de Physiopathologie & Pharmacologie Articulaires (LPPA), Vandœuvre-lès-Nancy, France | Laboratoires Negma-Lerads, Toussus le Noble, Magny-lès-Hameaux, France
Note: [] Address for correspondence: Jean-Yves Jouzeau, UMR 7561 CNRS-Nancy-Université, Laboratoire de Physiopathologie & Pharmacologie Articulaires (LPPA), Vandœuvre-lès-Nancy, France. Tel.: +33 3 83 68 39 53; Fax: +33 3 83 68 39 59; E-mail: [email protected].
Abstract: The present work aimed to take advantage of the screening capacity of protein arrays to search for additional targets of rhein in interleukin (IL)-1-stimulated chondrocytes. Primary cultures of chondrocytes from osteoarthritic (OA) patients were stimulated for 24 and 48 h with 1 ng/ml of IL-1α, in the presence or absence of 10−5 M of rhein. Culture supernatants were analyzed with arrays membranes consisting of 120 antibodies directed against cytokines, chemokines, and angiogenic or growth factors and were controlled for 8 proteins by specific immuno-enzymatic assays (ELISA). Protein arrays showed that several CC or CXC chemokines, the growth factor GM-CSF, the cytokines IL-6, IL-7 and IL-10 (but unexpectedly not IL-1β or TNFα) and the adhesion molecule ICAM-1 were induced maximally by IL-1α. In IL-1-stimulated chondrocytes, rhein reduced slightly the production of MCP-1 and increased those of IL-1Ra, of the cytokine receptors sgp130, IL-6R, sTNFR I and R II, but also of some chemokines or ICAM-1. Specific ELISAs confirmed the effect of rhein on MCP-1, IL-1Ra, sgp130, IL-6R and sTNFR II but was discrepant for GROα and were always more sensitive than protein arrays to detect IL-1 effects such as IL-1Ra and TNFα release. The present data show that rhein modulated some IL-1-induced responses contributing possibly to its chondroprotective (IL-1Ra, MCP-1) or cytokine modifying (sTNFR II, sgp130) properties, but that protein arrays were poorly sensitive to check for IL-1- and/or rhein-induced changes.
Keywords: Rhein, osteoarthritis, cartilage, protein screening, pro-inflammatory cytokines, chemokines
DOI: 10.3233/BIR-2008-0484
Journal: Biorheology, vol. 45, no. 3-4, pp. 439-455, 2008
