Department of Clinical Sciences, Pediatrics, Umeå University, Umeå, Sweden.
Lipum AB, Umeå, Sweden.
PLoS One. 2023 Aug 11;18(8):e0289980. doi: 10.1371/journal.pone.0289980. eCollection 2023.
The bile salt-stimulated lipase (BSSL) was originally recognized as a lipolytic enzyme expressed by the exocrine pancreas and in some species, notably humans, the lactating mammary gland, being secreted into the duodenum and with the mother's milk, respectively. However, BSSL is also present in the blood and has been assigned additional functions, even beyond the gastrointestinal tract. Conventional BSSL knockout mice are protected from developing disease in animal models of arthritis, and antibodies directed towards BSSL prevent or mitigate disease in similar models. The aim of this study was to investigate the role of BSSL as a newly discovered player in inflammation and specifically in inflammatory joint disorders. As part of mechanism of action, we here show that BSSL is secreted by neutrophils, interacts with monocytes and stimulates their migration in vitro. An anti-BSSL antibody that blocks the human BSSL-monocyte interaction was shown to simultaneously prevent the signaling pathway by which BSSL induce cell migration. Moreover, in this cohort study we show that BSSL levels are significantly higher in blood samples from patients with rheumatoid arthritis and psoriatic arthritis compared to healthy controls. The BSSL levels in patients' blood also correlated with disease activity scores and established inflammatory markers. Hence, although the mode of action is not yet fully clarified, we conclude that BSSL could be considered a proinflammatory component in the innate immune system and thus a possible novel target for treatment of chronic inflammation.
胆汁盐刺激的脂肪酶（BSSL）最初被认为是一种由胰腺外分泌表达的脂肪酶，在某些物种中，特别是人类和哺乳期的乳腺，分别分泌到十二指肠和母乳中。然而，BSSL 也存在于血液中，并被赋予了额外的功能，甚至超越了胃肠道。传统的 BSSL 基因敲除小鼠在关节炎的动物模型中免受疾病的影响，而针对 BSSL 的抗体可预防或减轻类似模型中的疾病。本研究旨在探讨 BSSL 作为一种新发现的炎症因子，特别是在炎症性关节疾病中的作用。作为作用机制的一部分，我们在此表明 BSSL 由中性粒细胞分泌，与单核细胞相互作用并刺激其体外迁移。一种阻断人 BSSL-单核细胞相互作用的抗 BSSL 抗体被证明可以同时阻止 BSSL 诱导细胞迁移的信号通路。此外，在这项队列研究中，我们发现类风湿关节炎和银屑病关节炎患者的血液样本中 BSSL 水平明显高于健康对照组。患者血液中的 BSSL 水平也与疾病活动评分和既定的炎症标志物相关。因此，尽管作用机制尚未完全阐明，但我们得出结论，BSSL 可能被视为先天免疫系统中的促炎成分，因此可能成为慢性炎症治疗的新靶点。
