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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 on CXCL13 secretion in the murine air pouch with or without TNF-α pretreatment. (a) Six-day-old air pouches were produced in the dorsal skin of mice and injected with TNF-α or the vehicle for 16 h prior to stimulation with LPA for 2 h. The nontreated (NT) group was injected with vehicle only (PBS-BSA). The air pouch exudates (n = 3) were collected and pooled for qualitative analysis of cytokine/chemokine secretion using the Proteome Profiler Mouse Antibody Array Panel (a). (b) Normalized data representing CXCL13 pixel density are the mean from two independent experiments.
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fig1: Effect of LPA on CXCL13 secretion in the murine air pouch with or without TNF-α pretreatment. (a) Six-day-old air pouches were produced in the dorsal skin of mice and injected with TNF-α or the vehicle for 16 h prior to stimulation with LPA for 2 h. The nontreated (NT) group was injected with vehicle only (PBS-BSA). The air pouch exudates (n = 3) were collected and pooled for qualitative analysis of cytokine/chemokine secretion using the Proteome Profiler Mouse Antibody Array Panel (a). (b) Normalized data representing CXCL13 pixel density are the mean from two independent experiments.

Mentions: LPA injected into air pouches has been reported to induce the synthesis of multiple cytokines/chemokines including IL-6, IL-1β, IL-16, KC, IP-10, and MIP-2 [4, 11]. Whereas the chemokine CXCL1 (also named KC or Gro-α) plays a role in LPA-mediated leukocyte recruitment into the mouse air pouch, blocking CXCL1 or its receptor CXCR2 does not completely reduce leukocyte influx suggesting the involvement of other chemokines or inflammatory mediators [4, 11]. In this series of experiments we focused on LPA-induced CXCL13 secretion into the air pouches. As previously reported [11], injection of 3 μg LPA into the air pouch for 2 hours increases the secretion of CXCL13 as assessed using a qualitative mouse Cytokine/Chemokine Antibody Array assay (Figure 1(a)). Pretreatment of the air pouch tissues with TNF-α (50 ng) for 16 hours also increased the levels of CXCL-13 in the air pouch exudates relative to mice injected with vehicle alone. The combined effect of TNF-α pretreatment prior to LPA stimulation enhances CXCL13 synthesis as estimated by densitometry (Figure 1(b)).


LPA Promotes T Cell Recruitment through Synthesis of CXCL13.

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

Effect of LPA on CXCL13 secretion in the murine air pouch with or without TNF-α pretreatment. (a) Six-day-old air pouches were produced in the dorsal skin of mice and injected with TNF-α or the vehicle for 16 h prior to stimulation with LPA for 2 h. The nontreated (NT) group was injected with vehicle only (PBS-BSA). The air pouch exudates (n = 3) were collected and pooled for qualitative analysis of cytokine/chemokine secretion using the Proteome Profiler Mouse Antibody Array Panel (a). (b) Normalized data representing CXCL13 pixel density are the mean from two independent experiments.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4539179&req=5

fig1: Effect of LPA on CXCL13 secretion in the murine air pouch with or without TNF-α pretreatment. (a) Six-day-old air pouches were produced in the dorsal skin of mice and injected with TNF-α or the vehicle for 16 h prior to stimulation with LPA for 2 h. The nontreated (NT) group was injected with vehicle only (PBS-BSA). The air pouch exudates (n = 3) were collected and pooled for qualitative analysis of cytokine/chemokine secretion using the Proteome Profiler Mouse Antibody Array Panel (a). (b) Normalized data representing CXCL13 pixel density are the mean from two independent experiments.
Mentions: LPA injected into air pouches has been reported to induce the synthesis of multiple cytokines/chemokines including IL-6, IL-1β, IL-16, KC, IP-10, and MIP-2 [4, 11]. Whereas the chemokine CXCL1 (also named KC or Gro-α) plays a role in LPA-mediated leukocyte recruitment into the mouse air pouch, blocking CXCL1 or its receptor CXCR2 does not completely reduce leukocyte influx suggesting the involvement of other chemokines or inflammatory mediators [4, 11]. In this series of experiments we focused on LPA-induced CXCL13 secretion into the air pouches. As previously reported [11], injection of 3 μg LPA into the air pouch for 2 hours increases the secretion of CXCL13 as assessed using a qualitative mouse Cytokine/Chemokine Antibody Array assay (Figure 1(a)). Pretreatment of the air pouch tissues with TNF-α (50 ng) for 16 hours also increased the levels of CXCL-13 in the air pouch exudates relative to mice injected with vehicle alone. The combined effect of TNF-α pretreatment prior to LPA stimulation enhances CXCL13 synthesis as estimated by densitometry (Figure 1(b)).

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