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Infiltration of myeloid cells into decidua is a critical early event in the labour cascade and post-partum uterine remodelling.

Shynlova O, Nedd-Roderique T, Li Y, Dorogin A, Nguyen T, Lye SJ - J. Cell. Mol. Med. (2013)

Bottom Line: Flow cytometry revealed a significant (P < 0.05) increase in decidual Macs prior to TL; M and N numbers increased during TL and further increased during PP, which correlated with immunohistochemistry data.PP period following TL and PTL was associated with further up-regulation of multiple cytokines/chemokines (P < 0.05).Our data suggest a programme of myeloid cells involvement in parturition with the pre-partum influx of Macs into the decidua contributing to the progression of labour, whereas the later influx of M and N contribute to PP decidual involution.

View Article: PubMed Central - PubMed

Affiliation: Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada. shynlova@lunenfeld.ca

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Changes in cytokine mRNA levels in the mouse decidua during normal gestation, term labour and post-partum (TL group), LPS-induced PTL and post-partum (LPS PTL group) and RU486-induced PTL and post-partum (RU PTL group). (A) Pro-inflammatory (Il1b, Il6, Il12b, Tnf) and anti-inflammatory (Il10) cytokines; (B) Chemokines Ccl2 (Mcp1), Ccl3 (Mip1a), Ccl4 (Mip1b), Csf2 (Gmscf), Cxcl1 (KC or Groa) and Cxcl2 (Mip2a) mRNA expression were detected by Real-Time RT-PCR. Shown are samples collected from late pregnant mice (GD15, RU Vehicle or LPS Sham, white bars), GD18 (doted bars), GD19 (term not in labour, checkered bars), term and preterm labouring samples (grey bars) or decidual samples collected 2–6 hrs post-partum (black bars). Results were expressed as mean ± SEM (n = 4). Significant difference with GD15/RU486 Vehicle/Sham LPS is indicated by *P < 0.05 and **P < 0.01.
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fig03: Changes in cytokine mRNA levels in the mouse decidua during normal gestation, term labour and post-partum (TL group), LPS-induced PTL and post-partum (LPS PTL group) and RU486-induced PTL and post-partum (RU PTL group). (A) Pro-inflammatory (Il1b, Il6, Il12b, Tnf) and anti-inflammatory (Il10) cytokines; (B) Chemokines Ccl2 (Mcp1), Ccl3 (Mip1a), Ccl4 (Mip1b), Csf2 (Gmscf), Cxcl1 (KC or Groa) and Cxcl2 (Mip2a) mRNA expression were detected by Real-Time RT-PCR. Shown are samples collected from late pregnant mice (GD15, RU Vehicle or LPS Sham, white bars), GD18 (doted bars), GD19 (term not in labour, checkered bars), term and preterm labouring samples (grey bars) or decidual samples collected 2–6 hrs post-partum (black bars). Results were expressed as mean ± SEM (n = 4). Significant difference with GD15/RU486 Vehicle/Sham LPS is indicated by *P < 0.05 and **P < 0.01.

Mentions: The expression of multiple pro- and anti-inflammatory genes were evaluated by Real-Time PCR during late gestation, TL, and PP. Pro-inflammatory cytokines tumour necrosis factor-α (Tnf), interleukin (Il)1β (Il1b), Il6 and Il12 as well as two major neutrophil chemoattractants (C-X-C motif) ligand 1 (Cxcl1, also known as Neutrophil-activating protein 3 (NAP-3) or KC), Cxcl2 (also known as macrophage inflammatory protein 2-alpha, Mip2a) and monocyte chemoattractant (C-C motif) Ligand 2 (Ccl2, also known as monocyte chemoattractant protein-1, Mcp1) mRNA levels all were significantly up-regulated during labour and PP (Fig. 3, Table 2). Ccl4 (also known as Macrophage inflammatory protein 1 beta, Mip1b), Ccl3 (also known as Macrophage inflammatory protein 1 alpha, Mip1a) and anti-inflammatory cytokine Il10 genes were also increased during TL but significance was not reached due to a high variability between samples (Fig. 3A). Transcript levels of growth factor Csf2 (granulocyte–macrophage colony-stimulating factor) regulating neutrophil/monocyte differentiation increased in decidua PP 2–6 hrs after parturition (Fig. 3B). The expression of corresponding cytokine proteins partially confirmed changes in cytokine transcripts. Using multiplex protein assay we detected a significant increase in decidual IL1b and IL6 pro-inflammatory cytokines and Ccl2 chemokine during TL and PP (P < 0.05, Fig. 4, Table 3). CXCL1 protein was only increased PP (P < 0.05) whereas no change in the protein level of TNFα, IL10 and CSF2 was observed (Fig. 4, Table 3).


Infiltration of myeloid cells into decidua is a critical early event in the labour cascade and post-partum uterine remodelling.

Shynlova O, Nedd-Roderique T, Li Y, Dorogin A, Nguyen T, Lye SJ - J. Cell. Mol. Med. (2013)

Changes in cytokine mRNA levels in the mouse decidua during normal gestation, term labour and post-partum (TL group), LPS-induced PTL and post-partum (LPS PTL group) and RU486-induced PTL and post-partum (RU PTL group). (A) Pro-inflammatory (Il1b, Il6, Il12b, Tnf) and anti-inflammatory (Il10) cytokines; (B) Chemokines Ccl2 (Mcp1), Ccl3 (Mip1a), Ccl4 (Mip1b), Csf2 (Gmscf), Cxcl1 (KC or Groa) and Cxcl2 (Mip2a) mRNA expression were detected by Real-Time RT-PCR. Shown are samples collected from late pregnant mice (GD15, RU Vehicle or LPS Sham, white bars), GD18 (doted bars), GD19 (term not in labour, checkered bars), term and preterm labouring samples (grey bars) or decidual samples collected 2–6 hrs post-partum (black bars). Results were expressed as mean ± SEM (n = 4). Significant difference with GD15/RU486 Vehicle/Sham LPS is indicated by *P < 0.05 and **P < 0.01.
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getmorefigures.php?uid=PMC3822594&req=5

fig03: Changes in cytokine mRNA levels in the mouse decidua during normal gestation, term labour and post-partum (TL group), LPS-induced PTL and post-partum (LPS PTL group) and RU486-induced PTL and post-partum (RU PTL group). (A) Pro-inflammatory (Il1b, Il6, Il12b, Tnf) and anti-inflammatory (Il10) cytokines; (B) Chemokines Ccl2 (Mcp1), Ccl3 (Mip1a), Ccl4 (Mip1b), Csf2 (Gmscf), Cxcl1 (KC or Groa) and Cxcl2 (Mip2a) mRNA expression were detected by Real-Time RT-PCR. Shown are samples collected from late pregnant mice (GD15, RU Vehicle or LPS Sham, white bars), GD18 (doted bars), GD19 (term not in labour, checkered bars), term and preterm labouring samples (grey bars) or decidual samples collected 2–6 hrs post-partum (black bars). Results were expressed as mean ± SEM (n = 4). Significant difference with GD15/RU486 Vehicle/Sham LPS is indicated by *P < 0.05 and **P < 0.01.
Mentions: The expression of multiple pro- and anti-inflammatory genes were evaluated by Real-Time PCR during late gestation, TL, and PP. Pro-inflammatory cytokines tumour necrosis factor-α (Tnf), interleukin (Il)1β (Il1b), Il6 and Il12 as well as two major neutrophil chemoattractants (C-X-C motif) ligand 1 (Cxcl1, also known as Neutrophil-activating protein 3 (NAP-3) or KC), Cxcl2 (also known as macrophage inflammatory protein 2-alpha, Mip2a) and monocyte chemoattractant (C-C motif) Ligand 2 (Ccl2, also known as monocyte chemoattractant protein-1, Mcp1) mRNA levels all were significantly up-regulated during labour and PP (Fig. 3, Table 2). Ccl4 (also known as Macrophage inflammatory protein 1 beta, Mip1b), Ccl3 (also known as Macrophage inflammatory protein 1 alpha, Mip1a) and anti-inflammatory cytokine Il10 genes were also increased during TL but significance was not reached due to a high variability between samples (Fig. 3A). Transcript levels of growth factor Csf2 (granulocyte–macrophage colony-stimulating factor) regulating neutrophil/monocyte differentiation increased in decidua PP 2–6 hrs after parturition (Fig. 3B). The expression of corresponding cytokine proteins partially confirmed changes in cytokine transcripts. Using multiplex protein assay we detected a significant increase in decidual IL1b and IL6 pro-inflammatory cytokines and Ccl2 chemokine during TL and PP (P < 0.05, Fig. 4, Table 3). CXCL1 protein was only increased PP (P < 0.05) whereas no change in the protein level of TNFα, IL10 and CSF2 was observed (Fig. 4, Table 3).

Bottom Line: Flow cytometry revealed a significant (P < 0.05) increase in decidual Macs prior to TL; M and N numbers increased during TL and further increased during PP, which correlated with immunohistochemistry data.PP period following TL and PTL was associated with further up-regulation of multiple cytokines/chemokines (P < 0.05).Our data suggest a programme of myeloid cells involvement in parturition with the pre-partum influx of Macs into the decidua contributing to the progression of labour, whereas the later influx of M and N contribute to PP decidual involution.

View Article: PubMed Central - PubMed

Affiliation: Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada. shynlova@lunenfeld.ca

Show MeSH
Related in: MedlinePlus