Bile Salt-Stimulated Lipase Plays an Unexpected Role in Arthritis Development in Rodents

Abstract

ObjectiveThe 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.MethodsCollagen-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.ResultsIn 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.ConclusionOur data strongly support BSSL as a key player in the inflammatory process, at least in rodents. It also suggests the possibility that BSSL-neutralizing agents could serve as a therapeutic model to reduce the inflammatory response in humans.

Effects of bile salt-stimulated lipase on blood cells and associations with disease activity in human inflammatory joint disorders

“…The BSSL protein has previously been recognized as an important player in the inflammatory process of arthritis in rodents [15]. The data presented here clearly demonstrates that BSSL is also closely associated with inflammatory joint diseases in humans.…”

“…In addition to its roles in dietary fat digestion and protection against viral infections, BSSL has been discovered as an essential player in inflammatory arthritis [15]. Conventional BSSL knockout mice are significantly less prone to develop collagen-induced arthritis (CIA) compared to wildtype littermates, and antibodies directed towards BSSL has been shown to mitigate disease activity in two different species and experimental models of arthritis, i.e.…”

“…Conventional BSSL knockout mice are significantly less prone to develop collagen-induced arthritis (CIA) compared to wildtype littermates, and antibodies directed towards BSSL has been shown to mitigate disease activity in two different species and experimental models of arthritis, i.e. CIA in mice and pristane-induced arthritis in rats [15]. We hypothesized that BSSL is involved in the inflammatory process not only in rodents, but also in patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) and envision humanized anti-BSSL antibodies to be as a novel therapy to combat arthritis.…”

rhBSSL Improves Growth and LCPUFA Absorption in Preterm Infants Fed Formula or Pasteurized Breast Milk

“…It is expressed in the exocrine pancreas and secreted into the intestinal lumen and is primarily acknowledged for its function in facilitating digestion and absorption of dietary fat. BSSL is also found in blood, but its role in the circulation is less clear (19). In the gastrointestinal (GI) tract, BSSL has broad specificity and hydrolyzes a variety of different substrates, for example, tri-, di-, and monoglycerides, cholesteryl and retinyl esters, phospholipids, and ceramides (20)(21)(22).…”

Activation of bile salt dependent lipase by (lyso)phosphatidic acid and platelet activating factor

“…Besides this digestive function, growing data points out that this enzyme could have an important extraintestinal function: BSDL was found to be able to traverse the intestinal mucosa towards blood circulation and was even retrieved in urines of healthy subjects [10][11][12]; it is secreted by endothelial cells and monocytes-macrophages [13,14] and several studies supported its involvement in the metabolism of lipoproteins, with impact on the cholesterol pools [15][16][17]. In link with this, it was reported that BSDL is or could be involved in pathophysiological processes, including atherosclerosis and inflammation [18][19][20][21][22][23].…”