bile salt-stimulated lipase plays an unexpected role in arthritis development in rodents胆汁salt-stimulated脂肪酶在啮齿动物关节炎发展起到了意想不到的作用.pdf

Bile Salt-Stimulated Lipase Plays an Unexpected Role in Arthritis Development in Rodents Susanne Lindquist*, Eva-Lotta Andersson, Lennart Lundberg, Olle Hernell ˚ ˚ Department of Clinical Sciences, Pediatrics, Umea University, Umea, Sweden Abstract Objective: The present study aimed to explore the hypothesis that bile salt-stimulated lipase (BSSL), in addition to being a key enzyme in dietary fat digestion during early infancy, plays an important role in inflammation, notably arthritis. Methods: Collagen-induced arthritis (CIA) and pristane-induced arthritis (PIA) in rodents are commonly used experimental models that reproduce many of the pathogenic mechanisms of human rheumatoid arthritis, i.e. increased cellular infiltration, synovial hyperplasia, pannus formation, and erosion of cartilage and bone in the distal joints. We used the CIA model to compare the response in BSSL wild type (BSSL-WT) mice with BSSL-deficient ‘knock-out’ (BSSL-KO) and BSSL- heterozygous (BSSL-HET) littermates. We also investigated if intraperitoneal injection of BSSL-neutralizing antibodies affected the development or severity of CIA and PIA in mice and rats, respectively. Results: In two consecutive studies, we found that BSSL-KO male mice, in contrast to BSSL-WT littermates, were significantly protected from developing arthritis. We also found that BSSL-HET mice were less prone to develop disease compared to BSSL-WT mice, but not as resistant as BSSL-KO mice, suggesting a gene-dose effect. Moreover, we found that BSSL- neutralizing antibody injection reduced both the incidence and severity of CIA and PIA in rodents. Conclusion: Our data strongly support BSSL as a key player in the inflammatory process, at