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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.

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Related in: MedlinePlus

LPS-responsivity in peritoneal macrophages isolated from the fat-1 or wild type mice.Peritoneal macrophages were isolated from untreated wild-type (black) and fat-1 (white) mice by positive magnetic bead selection. Isolated macrophages were exposed to LPS in the condition medium. Total RNA was extracted from the macrophages 0, 1, 3 hours after LPS exposure. ΙL−6 (A) and IL−1β (B) mRNA levels were measured by RT-qPCR, normalized to β-actin and plotted against time after LPS exposure (0, 1, or 3 hours). Mean mRNA levels and standard deviations are shown. Asterisks indicate those comparisons (wild type vs. fat-1 mice) with statistical significance (p < 0.05). (n = 8).
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f3: LPS-responsivity in peritoneal macrophages isolated from the fat-1 or wild type mice.Peritoneal macrophages were isolated from untreated wild-type (black) and fat-1 (white) mice by positive magnetic bead selection. Isolated macrophages were exposed to LPS in the condition medium. Total RNA was extracted from the macrophages 0, 1, 3 hours after LPS exposure. ΙL−6 (A) and IL−1β (B) mRNA levels were measured by RT-qPCR, normalized to β-actin and plotted against time after LPS exposure (0, 1, or 3 hours). Mean mRNA levels and standard deviations are shown. Asterisks indicate those comparisons (wild type vs. fat-1 mice) with statistical significance (p < 0.05). (n = 8).

Mentions: Next, we assessed the responsiveness of peritoneal macrophages to LPS and made comparisons between fat-1 and wild type mice. Peritoneal macrophages were isolated from the peritoneal cells of untreated fat-1 or wild type mice. Collected macrophages were exposed to LPS in the conditioned medium and collected after 0, 1 and 3 hours of exposure. Macrophage IL-6 and IL-1β mRNA levels were measured by RT-qPCR at each time point (Fig. 3). At baseline (0 hours), macrophages derived from fat-1 and from wild type mice had equal IL-6 and IL-1β mRNA levels. Macrophage IL-6 and IL-1β mRNA levels in wild type mice increased in a manner dependent on LPS exposure time. No significant increases in IL-6 and IL-1β mRNA levels were detected in the macrophages derived from fat-1 mice. In fact, IL-1β mRNA levels in the macrophage derived from fat-1 mice after 3 hours of exposure were markedly lower than those in wild type murine macrophages.


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)

LPS-responsivity in peritoneal macrophages isolated from the fat-1 or wild type mice.Peritoneal macrophages were isolated from untreated wild-type (black) and fat-1 (white) mice by positive magnetic bead selection. Isolated macrophages were exposed to LPS in the condition medium. Total RNA was extracted from the macrophages 0, 1, 3 hours after LPS exposure. ΙL−6 (A) and IL−1β (B) mRNA levels were measured by RT-qPCR, normalized to β-actin and plotted against time after LPS exposure (0, 1, or 3 hours). Mean mRNA levels and standard deviations are shown. Asterisks indicate those comparisons (wild type vs. fat-1 mice) with statistical significance (p < 0.05). (n = 8).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f3: LPS-responsivity in peritoneal macrophages isolated from the fat-1 or wild type mice.Peritoneal macrophages were isolated from untreated wild-type (black) and fat-1 (white) mice by positive magnetic bead selection. Isolated macrophages were exposed to LPS in the condition medium. Total RNA was extracted from the macrophages 0, 1, 3 hours after LPS exposure. ΙL−6 (A) and IL−1β (B) mRNA levels were measured by RT-qPCR, normalized to β-actin and plotted against time after LPS exposure (0, 1, or 3 hours). Mean mRNA levels and standard deviations are shown. Asterisks indicate those comparisons (wild type vs. fat-1 mice) with statistical significance (p < 0.05). (n = 8).
Mentions: Next, we assessed the responsiveness of peritoneal macrophages to LPS and made comparisons between fat-1 and wild type mice. Peritoneal macrophages were isolated from the peritoneal cells of untreated fat-1 or wild type mice. Collected macrophages were exposed to LPS in the conditioned medium and collected after 0, 1 and 3 hours of exposure. Macrophage IL-6 and IL-1β mRNA levels were measured by RT-qPCR at each time point (Fig. 3). At baseline (0 hours), macrophages derived from fat-1 and from wild type mice had equal IL-6 and IL-1β mRNA levels. Macrophage IL-6 and IL-1β mRNA levels in wild type mice increased in a manner dependent on LPS exposure time. No significant increases in IL-6 and IL-1β mRNA levels were detected in the macrophages derived from fat-1 mice. In fact, IL-1β mRNA levels in the macrophage derived from fat-1 mice after 3 hours of exposure were markedly lower than those in wild type murine macrophages.

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
Related in: MedlinePlus