Limits...
Increased tissue levels of omega-3 polyunsaturated fatty acids prevents pathological preterm birth.

Yamashita A, Kawana K, Tomio K, Taguchi A, Isobe Y, Iwamoto R, Masuda K, Furuya H, Nagamatsu T, Nagasaka K, Arimoto T, Oda K, Wada-Hiraike O, Yamashita T, Taketani Y, Kang JX, Kozuma S, Arai H, Arita M, Osuga Y, Fujii T - Sci Rep (2013)

Bottom Line: Omega-3 polyunsaturated fatty acids such as eicosapentaenoic acid (EPA) have anti-inflammatory effects.Preterm birth is an important problem in modern obstetrics and one of the main causes is an inflammation.Our data suggest that RvE3 could be a potential new therapeutic for the prevention of preterm birth.

View Article: PubMed Central - PubMed

Affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.

ABSTRACT
Omega-3 polyunsaturated fatty acids such as eicosapentaenoic acid (EPA) have anti-inflammatory effects. Preterm birth is an important problem in modern obstetrics and one of the main causes is an inflammation. We here showed that abundance of omega-3 fatty acids reduced the incidence of preterm birth induced by LPS with fat-1 mice, capable of converting omega-6 to omega-3 fatty acids. We also indicated that the gene expression of IL-6 and IL-1β in uteruses and the number of cervical infiltrating macrophages were reduced in fat-1 mice. The analyses of lipid metabolomics showed the high level of 18-hydroxyeicosapentaenoate in fat-1 mice, which was derived from EPA and was metabolized to anti-inflammatory product named resolvin E3 (RvE3). We finally showed that the administration of RvE3 to LPS-exposed pregnant wild type mice lowered the incidence of preterm birth. Our data suggest that RvE3 could be a potential new therapeutic for the prevention of preterm birth.

Show MeSH
Induction of pro-inflammatory cytokines by LPS intracervical LPS.LPS (15 microgram) or saline was injected into the cervices of pregnant fat-1 or wild type mice at 15 days of gestation. The uteri of injected mice were harvested six hours after LPS-injection and total RNA was extracted. mRNA levels of IL-6 (A), IL-1β (B), and TNF-α (C) were measured using RT-qPCR. Comparisons were made between wild-type (black) and fat-1 (white) animals. IL-6, IL-1β and TNF-α mRNA levels were normalized to β-actin. Mean mRNA levels and standard deviations were plotted. Asterisks indicate those comparisons (wild type vs. fat-1 mice) with statistical significance (p < 0.05). (n = 4).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3814804&req=5

f1: Induction of pro-inflammatory cytokines by LPS intracervical LPS.LPS (15 microgram) or saline was injected into the cervices of pregnant fat-1 or wild type mice at 15 days of gestation. The uteri of injected mice were harvested six hours after LPS-injection and total RNA was extracted. mRNA levels of IL-6 (A), IL-1β (B), and TNF-α (C) were measured using RT-qPCR. Comparisons were made between wild-type (black) and fat-1 (white) animals. IL-6, IL-1β and TNF-α mRNA levels were normalized to β-actin. Mean mRNA levels and standard deviations were plotted. Asterisks indicate those comparisons (wild type vs. fat-1 mice) with statistical significance (p < 0.05). (n = 4).

Mentions: The mechanisms underlying LPS-induced preterm birth are reported to include LPS-induced local pro-inflammatory cytokine production, cytokine-mediated elevations in the production of PGE2 and PGF2α and, ultimately, uterine contraction, cervical ripening and preterm delivery567. All of these cascades occur in the placenta and the uterine myometrium. We hypothesized that the anti-inflammatory effects of omega-3 PUFAs may suppress LPS-induced local inflammation and PGE2 and PGF2α production within the uterus. Pregnant fat-1 and wild type mice were injected transvaginally and intracervically with 15 μg/head of LPS or saline. The myometria of exposed animals were collected six hours after injection. The local production of the pro-inflammatory cytokines, IL-6, IL-1β, and TNFα, which are known to be involved in the mechanism of preterm birth22232425, were quantitated in all animals and compared between groups. As reported previously, the production of IL-6, IL-1β, and TNFα was induced in the myometria of all LPS-injected mice. IL-6 and IL-1β mRNA levels in fat-1 mice were significantly lower than those in wild type mice, but no differences in TNF-α mRNA levels were noted (Fig. 1). Fat-1 mice appeared to be at least partially resistant to the induction of pro-inflammatory cytokine production in myometrial tissues upon LPS exposure.


Increased tissue levels of omega-3 polyunsaturated fatty acids prevents pathological preterm birth.

Yamashita A, Kawana K, Tomio K, Taguchi A, Isobe Y, Iwamoto R, Masuda K, Furuya H, Nagamatsu T, Nagasaka K, Arimoto T, Oda K, Wada-Hiraike O, Yamashita T, Taketani Y, Kang JX, Kozuma S, Arai H, Arita M, Osuga Y, Fujii T - Sci Rep (2013)

Induction of pro-inflammatory cytokines by LPS intracervical LPS.LPS (15 microgram) or saline was injected into the cervices of pregnant fat-1 or wild type mice at 15 days of gestation. The uteri of injected mice were harvested six hours after LPS-injection and total RNA was extracted. mRNA levels of IL-6 (A), IL-1β (B), and TNF-α (C) were measured using RT-qPCR. Comparisons were made between wild-type (black) and fat-1 (white) animals. IL-6, IL-1β and TNF-α mRNA levels were normalized to β-actin. Mean mRNA levels and standard deviations were plotted. Asterisks indicate those comparisons (wild type vs. fat-1 mice) with statistical significance (p < 0.05). (n = 4).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3814804&req=5

f1: Induction of pro-inflammatory cytokines by LPS intracervical LPS.LPS (15 microgram) or saline was injected into the cervices of pregnant fat-1 or wild type mice at 15 days of gestation. The uteri of injected mice were harvested six hours after LPS-injection and total RNA was extracted. mRNA levels of IL-6 (A), IL-1β (B), and TNF-α (C) were measured using RT-qPCR. Comparisons were made between wild-type (black) and fat-1 (white) animals. IL-6, IL-1β and TNF-α mRNA levels were normalized to β-actin. Mean mRNA levels and standard deviations were plotted. Asterisks indicate those comparisons (wild type vs. fat-1 mice) with statistical significance (p < 0.05). (n = 4).
Mentions: The mechanisms underlying LPS-induced preterm birth are reported to include LPS-induced local pro-inflammatory cytokine production, cytokine-mediated elevations in the production of PGE2 and PGF2α and, ultimately, uterine contraction, cervical ripening and preterm delivery567. All of these cascades occur in the placenta and the uterine myometrium. We hypothesized that the anti-inflammatory effects of omega-3 PUFAs may suppress LPS-induced local inflammation and PGE2 and PGF2α production within the uterus. Pregnant fat-1 and wild type mice were injected transvaginally and intracervically with 15 μg/head of LPS or saline. The myometria of exposed animals were collected six hours after injection. The local production of the pro-inflammatory cytokines, IL-6, IL-1β, and TNFα, which are known to be involved in the mechanism of preterm birth22232425, were quantitated in all animals and compared between groups. As reported previously, the production of IL-6, IL-1β, and TNFα was induced in the myometria of all LPS-injected mice. IL-6 and IL-1β mRNA levels in fat-1 mice were significantly lower than those in wild type mice, but no differences in TNF-α mRNA levels were noted (Fig. 1). Fat-1 mice appeared to be at least partially resistant to the induction of pro-inflammatory cytokine production in myometrial tissues upon LPS exposure.

Bottom Line: Omega-3 polyunsaturated fatty acids such as eicosapentaenoic acid (EPA) have anti-inflammatory effects.Preterm birth is an important problem in modern obstetrics and one of the main causes is an inflammation.Our data suggest that RvE3 could be a potential new therapeutic for the prevention of preterm birth.

View Article: PubMed Central - PubMed

Affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.

ABSTRACT
Omega-3 polyunsaturated fatty acids such as eicosapentaenoic acid (EPA) have anti-inflammatory effects. Preterm birth is an important problem in modern obstetrics and one of the main causes is an inflammation. We here showed that abundance of omega-3 fatty acids reduced the incidence of preterm birth induced by LPS with fat-1 mice, capable of converting omega-6 to omega-3 fatty acids. We also indicated that the gene expression of IL-6 and IL-1β in uteruses and the number of cervical infiltrating macrophages were reduced in fat-1 mice. The analyses of lipid metabolomics showed the high level of 18-hydroxyeicosapentaenoate in fat-1 mice, which was derived from EPA and was metabolized to anti-inflammatory product named resolvin E3 (RvE3). We finally showed that the administration of RvE3 to LPS-exposed pregnant wild type mice lowered the incidence of preterm birth. Our data suggest that RvE3 could be a potential new therapeutic for the prevention of preterm birth.

Show MeSH