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Novel biphasic role of resolvin D1 on expression of cyclooxygenase-2 in lipopolysaccharide-stimulated lung fibroblasts is partly through PI3K/AKT and ERK2 pathways.

Wu D, Zheng S, Li W, Yang L, Liu Y, Zheng X, Yang Y, Yang L, Wang Q, Smith FG, Jin S - Mediators Inflamm. (2013)

Bottom Line: However, no significant change in the protein expression of COX-1 was observed after treatment with LPS in lung fibroblasts.In contrast, exogenous resolvin D1 increased the second peak of COX-2 expression as well as the production of PGD2 induced by LPS.In addition, resolvin D1 inhibited COX-2 expression at 6 hours, which was partly through PI3K/AKT and ERK2 signalling pathways.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesia and Critical Care, Second Affiliated Hospital of Wenzhou Medical University, 109 Xueyuan Road, Wenzhou, Zhejiang Province 325027, China.

ABSTRACT
Fibroblasts, far from being merely bystander cells, are known to play a specific role in inflammation resolution after an acute injury. As the endogenous "braking signal," resolvins possess potent anti-inflammatory and pro-resolution actions. We demonstrated that the expression of COX-2 protein was significantly peaked initially at 6 hours but then also at 48 hours after LPS stimulation in lung fibroblasts. PGE2 levels also peaked at 6 hours, and PGD2 levels were increased and peaked at 48 hours. However, no significant change in the protein expression of COX-1 was observed after treatment with LPS in lung fibroblasts. Exogenous resolvin D1 inhibited the first peak of COX-2 expression as well as the production of PGE2 induced by LPS. In contrast, exogenous resolvin D1 increased the second peak of COX-2 expression as well as the production of PGD2 induced by LPS. In addition, resolvin D1 inhibited COX-2 expression at 6 hours, which was partly through PI3K/AKT and ERK2 signalling pathways.

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COX-2 protein expression is partly through the activation of ERK1/2 and PI3K/AKT signaling pathways in primary rat lung fibroblasts stimulated with LPS. ((a1), (a2)) COX-2 protein expression induced by LPS in primary rat lung fibroblasts at 6 hours (the first COX-2 expression peak) was suppressed by inhibitors of PI3K/AKT (LY294002) and ERK1/2 (UO126) (∗P < 0.05 versus control, LPS + LY294002, LPS + UO126, LY294002, and UO126 groups). There is no significant change between control, LY294002, and UO126 groups (P > 0.05). ((b1), (b2)) COX-2 protein expression induced by LPS in primary rat lung fibroblasts at 48 hours (the second COX-2 expression peak) was not suppressed by inhibitors of PI3K/AKT (LY294002) and ERK1/2 (UO126) (∗P < 0.05 versus control, LY294002, and UO126 groups). There is no significant change between LPS, LPS + LY294002 and LPS + UO126 groups (P > 0.05). All experiments were repeated in triplicate.
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fig4: COX-2 protein expression is partly through the activation of ERK1/2 and PI3K/AKT signaling pathways in primary rat lung fibroblasts stimulated with LPS. ((a1), (a2)) COX-2 protein expression induced by LPS in primary rat lung fibroblasts at 6 hours (the first COX-2 expression peak) was suppressed by inhibitors of PI3K/AKT (LY294002) and ERK1/2 (UO126) (∗P < 0.05 versus control, LPS + LY294002, LPS + UO126, LY294002, and UO126 groups). There is no significant change between control, LY294002, and UO126 groups (P > 0.05). ((b1), (b2)) COX-2 protein expression induced by LPS in primary rat lung fibroblasts at 48 hours (the second COX-2 expression peak) was not suppressed by inhibitors of PI3K/AKT (LY294002) and ERK1/2 (UO126) (∗P < 0.05 versus control, LY294002, and UO126 groups). There is no significant change between LPS, LPS + LY294002 and LPS + UO126 groups (P > 0.05). All experiments were repeated in triplicate.

Mentions: Lipopolysaccharide (LPS) activates intracellular signalling pathways of a remarkable complexity [29], including activation of PI3K/AKT and ERK1/2 signaling pathways in fibroblasts [30]. To determine whether LPS-induced COX-2 expression in primary rat lung fibroblasts is through the activation of ERK1/2 and PI3K/AKT signaling pathways, we assessed the effects of specific inhibitors of ERK1/2 and PI3K/AKT on COX-2 protein expression. We found that COX-2 protein expression induced by LPS in primary rat lung fibroblasts at 6 hours (the first COX-2 expression peak) was suppressed by inhibitors of PI3K/AKT (LY294002) and ERK1/2 (UO126) (∗P < 0.05 versus control, LPS + LY294002, LPS + UO126, LY294002, and UO126 groups). There is no significant change between control, LY294002 and UO126 groups (P > 0.05) (Figure 4(a1, b1)), whereas COX-2 protein expression induced by LPS in primary rat lung fibroblasts at 48 hours (the second COX-2 expression peak) was not suppressed by inhibitors of PI3K/AKT (LY294002) and ERK1/2 (UO126) (∗P < 0.05 versus control, LY294002 and UO126 groups). There is no significant change between LPS, LPS + LY294002, and LPS + UO126 groups (P > 0.05) (Figure 4(a2, b2)).


Novel biphasic role of resolvin D1 on expression of cyclooxygenase-2 in lipopolysaccharide-stimulated lung fibroblasts is partly through PI3K/AKT and ERK2 pathways.

Wu D, Zheng S, Li W, Yang L, Liu Y, Zheng X, Yang Y, Yang L, Wang Q, Smith FG, Jin S - Mediators Inflamm. (2013)

COX-2 protein expression is partly through the activation of ERK1/2 and PI3K/AKT signaling pathways in primary rat lung fibroblasts stimulated with LPS. ((a1), (a2)) COX-2 protein expression induced by LPS in primary rat lung fibroblasts at 6 hours (the first COX-2 expression peak) was suppressed by inhibitors of PI3K/AKT (LY294002) and ERK1/2 (UO126) (∗P < 0.05 versus control, LPS + LY294002, LPS + UO126, LY294002, and UO126 groups). There is no significant change between control, LY294002, and UO126 groups (P > 0.05). ((b1), (b2)) COX-2 protein expression induced by LPS in primary rat lung fibroblasts at 48 hours (the second COX-2 expression peak) was not suppressed by inhibitors of PI3K/AKT (LY294002) and ERK1/2 (UO126) (∗P < 0.05 versus control, LY294002, and UO126 groups). There is no significant change between LPS, LPS + LY294002 and LPS + UO126 groups (P > 0.05). All experiments were repeated in triplicate.
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Related In: Results  -  Collection

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fig4: COX-2 protein expression is partly through the activation of ERK1/2 and PI3K/AKT signaling pathways in primary rat lung fibroblasts stimulated with LPS. ((a1), (a2)) COX-2 protein expression induced by LPS in primary rat lung fibroblasts at 6 hours (the first COX-2 expression peak) was suppressed by inhibitors of PI3K/AKT (LY294002) and ERK1/2 (UO126) (∗P < 0.05 versus control, LPS + LY294002, LPS + UO126, LY294002, and UO126 groups). There is no significant change between control, LY294002, and UO126 groups (P > 0.05). ((b1), (b2)) COX-2 protein expression induced by LPS in primary rat lung fibroblasts at 48 hours (the second COX-2 expression peak) was not suppressed by inhibitors of PI3K/AKT (LY294002) and ERK1/2 (UO126) (∗P < 0.05 versus control, LY294002, and UO126 groups). There is no significant change between LPS, LPS + LY294002 and LPS + UO126 groups (P > 0.05). All experiments were repeated in triplicate.
Mentions: Lipopolysaccharide (LPS) activates intracellular signalling pathways of a remarkable complexity [29], including activation of PI3K/AKT and ERK1/2 signaling pathways in fibroblasts [30]. To determine whether LPS-induced COX-2 expression in primary rat lung fibroblasts is through the activation of ERK1/2 and PI3K/AKT signaling pathways, we assessed the effects of specific inhibitors of ERK1/2 and PI3K/AKT on COX-2 protein expression. We found that COX-2 protein expression induced by LPS in primary rat lung fibroblasts at 6 hours (the first COX-2 expression peak) was suppressed by inhibitors of PI3K/AKT (LY294002) and ERK1/2 (UO126) (∗P < 0.05 versus control, LPS + LY294002, LPS + UO126, LY294002, and UO126 groups). There is no significant change between control, LY294002 and UO126 groups (P > 0.05) (Figure 4(a1, b1)), whereas COX-2 protein expression induced by LPS in primary rat lung fibroblasts at 48 hours (the second COX-2 expression peak) was not suppressed by inhibitors of PI3K/AKT (LY294002) and ERK1/2 (UO126) (∗P < 0.05 versus control, LY294002 and UO126 groups). There is no significant change between LPS, LPS + LY294002, and LPS + UO126 groups (P > 0.05) (Figure 4(a2, b2)).

Bottom Line: However, no significant change in the protein expression of COX-1 was observed after treatment with LPS in lung fibroblasts.In contrast, exogenous resolvin D1 increased the second peak of COX-2 expression as well as the production of PGD2 induced by LPS.In addition, resolvin D1 inhibited COX-2 expression at 6 hours, which was partly through PI3K/AKT and ERK2 signalling pathways.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesia and Critical Care, Second Affiliated Hospital of Wenzhou Medical University, 109 Xueyuan Road, Wenzhou, Zhejiang Province 325027, China.

ABSTRACT
Fibroblasts, far from being merely bystander cells, are known to play a specific role in inflammation resolution after an acute injury. As the endogenous "braking signal," resolvins possess potent anti-inflammatory and pro-resolution actions. We demonstrated that the expression of COX-2 protein was significantly peaked initially at 6 hours but then also at 48 hours after LPS stimulation in lung fibroblasts. PGE2 levels also peaked at 6 hours, and PGD2 levels were increased and peaked at 48 hours. However, no significant change in the protein expression of COX-1 was observed after treatment with LPS in lung fibroblasts. Exogenous resolvin D1 inhibited the first peak of COX-2 expression as well as the production of PGE2 induced by LPS. In contrast, exogenous resolvin D1 increased the second peak of COX-2 expression as well as the production of PGD2 induced by LPS. In addition, resolvin D1 inhibited COX-2 expression at 6 hours, which was partly through PI3K/AKT and ERK2 signalling pathways.

Show MeSH
Related in: MedlinePlus