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LPA Promotes T Cell Recruitment through Synthesis of CXCL13.

Hui W, Zhao C, Bourgoin SG - Mediators Inflamm. (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Rheumatology and Immunology Research Center, CHU de Québec Research Center and Faculty of Medicine, Laval University, 2705 Laurier Boulevard, Québec, QC, Canada G1V 4G2.

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.

No MeSH data available.


Related in: MedlinePlus

Effect of LPA and TNF-α on CXCL13 secretion in the air pouch. (a), (b) Kinetics of LPA and of TNF-α-mediated CXCL13 secretion. (a) LPA (3 μg) or (b) TNF-α (50 ng) was injected into air pouches and air pouch exudates were collected at indicated times. (c) Kinetics of LPA-induced CXCL13 secretion in air pouches pretreated with TNF-α. TNF-α was injected 16 h before LPA stimulation. Air pouch exudates were collected at indicated times. (d) Comparison of LPA-mediated CXCL13 secretion in untreated and TNF-α-primed air pouches. TNF-α or vehicle was injected 16 h prior to administration of LPA for 2 h. Exudates were collected and cytokine/chemokine secretion was measured by ELISA. The nontreated (NT) groups were injected with vehicle only (PBS-BSA). Data are the mean ± SE from three independent experiments performed with at least five mice per group. ∗P < 0.05, ∗∗P < 0.01, and ∗∗∗P < 0.001.
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fig2: Effect of LPA and TNF-α on CXCL13 secretion in the air pouch. (a), (b) Kinetics of LPA and of TNF-α-mediated CXCL13 secretion. (a) LPA (3 μg) or (b) TNF-α (50 ng) was injected into air pouches and air pouch exudates were collected at indicated times. (c) Kinetics of LPA-induced CXCL13 secretion in air pouches pretreated with TNF-α. TNF-α was injected 16 h before LPA stimulation. Air pouch exudates were collected at indicated times. (d) Comparison of LPA-mediated CXCL13 secretion in untreated and TNF-α-primed air pouches. TNF-α or vehicle was injected 16 h prior to administration of LPA for 2 h. Exudates were collected and cytokine/chemokine secretion was measured by ELISA. The nontreated (NT) groups were injected with vehicle only (PBS-BSA). Data are the mean ± SE from three independent experiments performed with at least five mice per group. ∗P < 0.05, ∗∗P < 0.01, and ∗∗∗P < 0.001.

Mentions: ELISA was then used to accurately quantify the kinetics of CXCL13 secretion (Figure 2(a)). The release of CXCL13 was significantly increased at 30 min after LPA stimulation and remained elevated up to 4 hours, the last time tested. TNF-α injected into the air pouches also induced CXCL13 secretion in a time-dependent manner (Figure 2(b)). A significant increase in CXCL13 secretion was observed at 4 hours and reached a maximum at 12 hours after TNF-α treatment, after which it declined. Although not statistically significant, a trend for higher levels of CXCL13 in air pouch lavage fluids at 16 hours following TNF-α treatment was observed compared to mice injected with vehicle alone (Figures 2(b) and 2(c)). When air pouches were pretreated with TNF-α for 16 hours, LPA induced robust secretion of CXCL13, which peaked at 2–4 hours after LPA stimulation (Figure 2(c)). TNF-α injected into the air pouches prior to LPA stimulation for 2 hours greatly potentiated CXCL13 secretion compared to mice injected with TNF-α alone or LPA alone (Figure 2(d)).


LPA Promotes T Cell Recruitment through Synthesis of CXCL13.

Hui W, Zhao C, Bourgoin SG - Mediators Inflamm. (2015)

Effect of LPA and TNF-α on CXCL13 secretion in the air pouch. (a), (b) Kinetics of LPA and of TNF-α-mediated CXCL13 secretion. (a) LPA (3 μg) or (b) TNF-α (50 ng) was injected into air pouches and air pouch exudates were collected at indicated times. (c) Kinetics of LPA-induced CXCL13 secretion in air pouches pretreated with TNF-α. TNF-α was injected 16 h before LPA stimulation. Air pouch exudates were collected at indicated times. (d) Comparison of LPA-mediated CXCL13 secretion in untreated and TNF-α-primed air pouches. TNF-α or vehicle was injected 16 h prior to administration of LPA for 2 h. Exudates were collected and cytokine/chemokine secretion was measured by ELISA. The nontreated (NT) groups were injected with vehicle only (PBS-BSA). Data are the mean ± SE from three independent experiments performed with at least five mice per group. ∗P < 0.05, ∗∗P < 0.01, and ∗∗∗P < 0.001.
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig2: Effect of LPA and TNF-α on CXCL13 secretion in the air pouch. (a), (b) Kinetics of LPA and of TNF-α-mediated CXCL13 secretion. (a) LPA (3 μg) or (b) TNF-α (50 ng) was injected into air pouches and air pouch exudates were collected at indicated times. (c) Kinetics of LPA-induced CXCL13 secretion in air pouches pretreated with TNF-α. TNF-α was injected 16 h before LPA stimulation. Air pouch exudates were collected at indicated times. (d) Comparison of LPA-mediated CXCL13 secretion in untreated and TNF-α-primed air pouches. TNF-α or vehicle was injected 16 h prior to administration of LPA for 2 h. Exudates were collected and cytokine/chemokine secretion was measured by ELISA. The nontreated (NT) groups were injected with vehicle only (PBS-BSA). Data are the mean ± SE from three independent experiments performed with at least five mice per group. ∗P < 0.05, ∗∗P < 0.01, and ∗∗∗P < 0.001.
Mentions: ELISA was then used to accurately quantify the kinetics of CXCL13 secretion (Figure 2(a)). The release of CXCL13 was significantly increased at 30 min after LPA stimulation and remained elevated up to 4 hours, the last time tested. TNF-α injected into the air pouches also induced CXCL13 secretion in a time-dependent manner (Figure 2(b)). A significant increase in CXCL13 secretion was observed at 4 hours and reached a maximum at 12 hours after TNF-α treatment, after which it declined. Although not statistically significant, a trend for higher levels of CXCL13 in air pouch lavage fluids at 16 hours following TNF-α treatment was observed compared to mice injected with vehicle alone (Figures 2(b) and 2(c)). When air pouches were pretreated with TNF-α for 16 hours, LPA induced robust secretion of CXCL13, which peaked at 2–4 hours after LPA stimulation (Figure 2(c)). TNF-α injected into the air pouches prior to LPA stimulation for 2 hours greatly potentiated CXCL13 secretion compared to mice injected with TNF-α alone or LPA alone (Figure 2(d)).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Rheumatology and Immunology Research Center, CHU de Québec Research Center and Faculty of Medicine, Laval University, 2705 Laurier Boulevard, Québec, QC, Canada G1V 4G2.

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.

No MeSH data available.


Related in: MedlinePlus