Effectiveness of the soluble form of the @entity5003 receptor accessory protein as an inhibitor of XXXX in @entity1753 .

@entity32 @entity625 @entity39 @entity19 @entity5 @entity2681 @entity5003 @entity70923 @entity1753 @entity777 @entity42214 @entity2720
OBJECTIVE: To investigate whether the soluble form of @entity42214 (sIL-1RAcP), whose physiologic function remains to be established, can serve as a specific inhibitor of @entity5003 signaling in vitro, and to evaluate its applicability in @entity1753 ( @entity1753 ). METHODS: Soluble @entity42214 was cloned from @entity19 liver complementary DNA and expressed by the use of either an adenoviral vector (AdRGD) for sIL-1RAcP or a stable-transfected NIH3T3 fibroblast cell line. The ability of affinity-purified @entity70923 RAcP to inhibit @entity5003 signaling was tested on NF-kappaB luciferase reporter fibroblasts and quantified by luminometer. To investigate therapeutic efficacy, sIL-1RAcP was both locally (knee joint) and systemically overexpressed in collagen-immunized male DBA/1 @entity19 . Severity of @entity625 was monitored visually, and the pathologic process in the joint was examined histologically. Serum was obtained from @entity19 to quantify @entity777 and anti-bovine type II collagen (BCII) antibody levels. RESULTS: Incubation of the NF-kappaB reporter fibroblast with purified @entity70923 RAcP protein showed a marked reduction of @entity5003 -induced, but not @entity5 @entity39 factor-induced, NF-kappaB activation. This showed a novel role for @entity70923 RAcP as a specific inhibitor of @entity5003 signaling. Local transplantation of @entity70923 RAcP-producing NIH3T3 fibroblasts into the knee before onset of @entity1753 had little or no effect on general disease severity in these @entity19 . Histologic evaluation of the knee joints receiving @entity70923 RAcP cell transplantation showed a marked @entity32 and bone and cartilage @entity2681 . Local treatment with @entity70923 RAcP had no profound effect on serum levels of @entity777 and anti-BCII antibodies, which is indicative of the ongoing presence of @entity625 in @entity2720 . In contrast to local treatment, systemic treatment with the AdRGD for @entity70923 RAcP markedly ameliorated @entity1753 in all joints. CONCLUSION: In this study we demonstrated that @entity70923 RAcP is a biologically active and innovative inhibitor of @entity5003 , and treatment of @entity19 with @entity70923 RAcP had a profound prophylactic effect on @entity1753 .
