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Crosstalk between monocytes and myometrial smooth muscle in culture generates synergistic pro-inflammatory cytokine production and enhances myocyte contraction, with effects opposed by progesterone.

Rajagopal SP, Hutchinson JL, Dorward DA, Rossi AG, Norman JE - Mol. Hum. Reprod. (2015)

Bottom Line: The synergistic secretion of IL-6 and IL-8 from co-cultures was mediated in part by direct cell-cell contact, and by TNF.Both progesterone and IL-10 inhibited LPS-stimulated IL-6 and IL-8 secretion from co-cultures, while progesterone also inhibited chemokine secretion.These effects are all partially inhibited by progesterone.

View Article: PubMed Central - PubMed

Affiliation: MRC Centre for Reproductive Health, University of Edinburgh, Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK.

No MeSH data available.


Related in: MedlinePlus

IL-10 inhibited LPS-induced IL-6 and IL-8 secretion from PHM1-41/monocyte co-cultures and primary monocytes, but not from PHM1-41 cells alone. PHM1-41 cells were cultured alone, in co-culture with primary monocytes, in a 10:1 ratio, or primary monocytes were cultured alone, and treated with either LPS (100 ng/ml) or LPS and IL-10 (50 ng/ml) for 24 h, after which conditioned media was assayed by ELISA. (A) IL-6 secretion from PHM1-41 cells was increased by LPS, but not inhibited by co-treatment with IL-10. (B) IL-6 secretion from primary monocytes was increased by LPS, and inhibited by IL-10. (C) IL-6 secretion from PHM1-41/monocyte co-culture was increased by LPS, and inhibited by IL-10. A similar pattern was observed with IL-8, for (D) PHM1-41 cells alone, (E) primary monocytes alone and (F) co-culture. Data are shown as mean ± SEM, n = 5 independent experiments, conducted in triplicate. Data were analysed by one-way ANOVA and post hoc Tukey's multiple comparison, *P < 0.05, **P < 0.01.
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GAV027F8: IL-10 inhibited LPS-induced IL-6 and IL-8 secretion from PHM1-41/monocyte co-cultures and primary monocytes, but not from PHM1-41 cells alone. PHM1-41 cells were cultured alone, in co-culture with primary monocytes, in a 10:1 ratio, or primary monocytes were cultured alone, and treated with either LPS (100 ng/ml) or LPS and IL-10 (50 ng/ml) for 24 h, after which conditioned media was assayed by ELISA. (A) IL-6 secretion from PHM1-41 cells was increased by LPS, but not inhibited by co-treatment with IL-10. (B) IL-6 secretion from primary monocytes was increased by LPS, and inhibited by IL-10. (C) IL-6 secretion from PHM1-41/monocyte co-culture was increased by LPS, and inhibited by IL-10. A similar pattern was observed with IL-8, for (D) PHM1-41 cells alone, (E) primary monocytes alone and (F) co-culture. Data are shown as mean ± SEM, n = 5 independent experiments, conducted in triplicate. Data were analysed by one-way ANOVA and post hoc Tukey's multiple comparison, *P < 0.05, **P < 0.01.

Mentions: Finally, the classical anti-inflammatory cytokine IL-10 in this model was investigated. Use of this cytokine has been proposed as a treatment for PTL (Robertson et al., 2006; Bayraktar et al., 2009), and it is increased in amniotic fluid of women in PTL (Gotsch et al., 2008). Whilst IL-10 co-treatment had no significant effect on LPS-induced IL-6 and IL-8 secretion from PHM1-41 cells (Fig. 8A and D), the IL-6 and IL-8 releases in both LPS treated primary monocytes (P < 0.01 and P < 0.05, Fig. 8B and E) and PHM1-41/monocyte co-cultures were inhibited by IL-10 (P < 0.01 and P < 0.05, Fig. 8C and F). These data suggest that IL-10 influences cytokine release in the co-cultures through the action of monocytes.Figure 8


Crosstalk between monocytes and myometrial smooth muscle in culture generates synergistic pro-inflammatory cytokine production and enhances myocyte contraction, with effects opposed by progesterone.

Rajagopal SP, Hutchinson JL, Dorward DA, Rossi AG, Norman JE - Mol. Hum. Reprod. (2015)

IL-10 inhibited LPS-induced IL-6 and IL-8 secretion from PHM1-41/monocyte co-cultures and primary monocytes, but not from PHM1-41 cells alone. PHM1-41 cells were cultured alone, in co-culture with primary monocytes, in a 10:1 ratio, or primary monocytes were cultured alone, and treated with either LPS (100 ng/ml) or LPS and IL-10 (50 ng/ml) for 24 h, after which conditioned media was assayed by ELISA. (A) IL-6 secretion from PHM1-41 cells was increased by LPS, but not inhibited by co-treatment with IL-10. (B) IL-6 secretion from primary monocytes was increased by LPS, and inhibited by IL-10. (C) IL-6 secretion from PHM1-41/monocyte co-culture was increased by LPS, and inhibited by IL-10. A similar pattern was observed with IL-8, for (D) PHM1-41 cells alone, (E) primary monocytes alone and (F) co-culture. Data are shown as mean ± SEM, n = 5 independent experiments, conducted in triplicate. Data were analysed by one-way ANOVA and post hoc Tukey's multiple comparison, *P < 0.05, **P < 0.01.
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GAV027F8: IL-10 inhibited LPS-induced IL-6 and IL-8 secretion from PHM1-41/monocyte co-cultures and primary monocytes, but not from PHM1-41 cells alone. PHM1-41 cells were cultured alone, in co-culture with primary monocytes, in a 10:1 ratio, or primary monocytes were cultured alone, and treated with either LPS (100 ng/ml) or LPS and IL-10 (50 ng/ml) for 24 h, after which conditioned media was assayed by ELISA. (A) IL-6 secretion from PHM1-41 cells was increased by LPS, but not inhibited by co-treatment with IL-10. (B) IL-6 secretion from primary monocytes was increased by LPS, and inhibited by IL-10. (C) IL-6 secretion from PHM1-41/monocyte co-culture was increased by LPS, and inhibited by IL-10. A similar pattern was observed with IL-8, for (D) PHM1-41 cells alone, (E) primary monocytes alone and (F) co-culture. Data are shown as mean ± SEM, n = 5 independent experiments, conducted in triplicate. Data were analysed by one-way ANOVA and post hoc Tukey's multiple comparison, *P < 0.05, **P < 0.01.
Mentions: Finally, the classical anti-inflammatory cytokine IL-10 in this model was investigated. Use of this cytokine has been proposed as a treatment for PTL (Robertson et al., 2006; Bayraktar et al., 2009), and it is increased in amniotic fluid of women in PTL (Gotsch et al., 2008). Whilst IL-10 co-treatment had no significant effect on LPS-induced IL-6 and IL-8 secretion from PHM1-41 cells (Fig. 8A and D), the IL-6 and IL-8 releases in both LPS treated primary monocytes (P < 0.01 and P < 0.05, Fig. 8B and E) and PHM1-41/monocyte co-cultures were inhibited by IL-10 (P < 0.01 and P < 0.05, Fig. 8C and F). These data suggest that IL-10 influences cytokine release in the co-cultures through the action of monocytes.Figure 8

Bottom Line: The synergistic secretion of IL-6 and IL-8 from co-cultures was mediated in part by direct cell-cell contact, and by TNF.Both progesterone and IL-10 inhibited LPS-stimulated IL-6 and IL-8 secretion from co-cultures, while progesterone also inhibited chemokine secretion.These effects are all partially inhibited by progesterone.

View Article: PubMed Central - PubMed

Affiliation: MRC Centre for Reproductive Health, University of Edinburgh, Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK.

No MeSH data available.


Related in: MedlinePlus