Abstract
Lysophosphatidic acid (LPA) is a bioactive phospholipid playing an important role in various inflammatory diseases by inducing expression and secretion of many inflammatory cytokines/chemokines. Here we report in a murine air pouch model of inflammation that LPA induced CXCL13 secretion in a time-dependent manner and with exacerbation of the response when LPA was administered after a pretreatment with TNF-α, a key inflammatory cytokine. LPA mediates recruitment of leukocytes, including that of CD3+ cells into unprimed and TNF-α-primed air pouches. CXCL13 neutralization using a blocking antibody injected into air pouches prior to administration of LPA into TNF-α-primed air pouches decreased CD3+ cell influx. Our data highlight that LPA-mediated CXCL13 secretion plays a role in T cell recruitment and participates in regulation of the inflammatory response.
Highlights
Lysophosphatidic acid (LPA) is a bioactive phospholipid with a simple structure containing a three-carbon glycerol backbone and a single acyl side chain that can vary in length and saturation [1]
We demonstrate that LPA induces the recruitment of leukocytes including T lymphocytes into air pouches through a mechanism that is mostly dependent on CXCL13 synthesis
Using the mouse air pouch model of inflammation, we previously demonstrated that LPA promotes the influx of neutrophils and other leukocyte subtypes including macrophages/monocytes and lymphocytes through activation of two LPA receptors, LPA1 and LPA3 [11]
Summary
Lysophosphatidic acid (LPA) is a bioactive phospholipid with a simple structure containing a three-carbon glycerol backbone and a single acyl side chain that can vary in length and saturation [1]. Increasing numbers of studies show that LPA plays a role in various inflammatory diseases [4,5,6]. Elevated LPA levels were detected in several biological fluids collected from different animal models of inflammation or patients with inflammatory diseases [2, 7, 8]. Increased expression of the LPA producing enzyme autotaxin (ATX) has been reported in synovial tissues from patients with rheumatoid arthritis (RA) [8, 9]. CXCL8 is one of the leukocyte chemoattractant chemokines reported to be induced by LPA in fibroblast-like synoviocytes from RA patients [9], as well as various other cell types [12,13,14,15]
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