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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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Macrophage infiltration into myometria and cervices of LPS-injected fat-1 and wild type mice.(A) Immunostaining of the myometria and cervices of LPS- or saline-injected mice for F4/80, a pan macrophage marker. Macrophages were detected using a specific anti-F4/80 mAb (1:500) (lower panels). An isotype-matched control mAb was used as a negative control (lower panels) (200×). Results are representative of two to ten normal tissues for each site. (B) The number of F4/80-positive cells detected in all fields of the myometrium or cervix were counted for wild type (black) or fat-1 (white) mice. Asterisks indicate those comparisons (wild type vs. fat-1 mice) with statistical significance (p < 0.05).
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f2: Macrophage infiltration into myometria and cervices of LPS-injected fat-1 and wild type mice.(A) Immunostaining of the myometria and cervices of LPS- or saline-injected mice for F4/80, a pan macrophage marker. Macrophages were detected using a specific anti-F4/80 mAb (1:500) (lower panels). An isotype-matched control mAb was used as a negative control (lower panels) (200×). Results are representative of two to ten normal tissues for each site. (B) The number of F4/80-positive cells detected in all fields of the myometrium or cervix were counted for wild type (black) or fat-1 (white) mice. Asterisks indicate those comparisons (wild type vs. fat-1 mice) with statistical significance (p < 0.05).

Mentions: Of the leukocytes that may contribute to recruitment and amplification of inflammatory reactions, macrophages are the predominant immune cell subtype residing in the uterus26. Macrophages produce a variety of factors, including prostaglandins and cytokines, that regulate uterine contractile activity2527. We therefore studied the macrophages infiltrating the myometria and cervices of fat-1 and wild type mice using immunohistochemical detection of F4/80-immunoreactive cells (Fig. 2A). Infiltration of F4/80-immunoreactive macrophages into the myometrium was observed in both wild type and fat-1 mice exposed to LPS (Fig. 2A, left lower two panels). Cervical infiltrating macrophages were also observed in LPS-injected wild type mice (26 ± 5.7 macrophages per 10 microscope fields, n = 3) but were quite infrequent in LPS-injected fat-1 mice (11 ± 2.0 macrophages per 10 microscope fields, n = 3) (right, lower two panels). F4/80 positive macrophages were quantitated and comparisons were made between fat-1 and wild type mice (Fig. 2B). No differences were detected in the number of myometrial infiltrating macrophages in LPS-injected fat-1 and wild type mice. In contrast, the number of cervical infiltrating macrophages in fat-1 mice was significantly lower than that in the wild type mice.


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)

Macrophage infiltration into myometria and cervices of LPS-injected fat-1 and wild type mice.(A) Immunostaining of the myometria and cervices of LPS- or saline-injected mice for F4/80, a pan macrophage marker. Macrophages were detected using a specific anti-F4/80 mAb (1:500) (lower panels). An isotype-matched control mAb was used as a negative control (lower panels) (200×). Results are representative of two to ten normal tissues for each site. (B) The number of F4/80-positive cells detected in all fields of the myometrium or cervix were counted for wild type (black) or fat-1 (white) mice. Asterisks indicate those comparisons (wild type vs. fat-1 mice) with statistical significance (p < 0.05).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f2: Macrophage infiltration into myometria and cervices of LPS-injected fat-1 and wild type mice.(A) Immunostaining of the myometria and cervices of LPS- or saline-injected mice for F4/80, a pan macrophage marker. Macrophages were detected using a specific anti-F4/80 mAb (1:500) (lower panels). An isotype-matched control mAb was used as a negative control (lower panels) (200×). Results are representative of two to ten normal tissues for each site. (B) The number of F4/80-positive cells detected in all fields of the myometrium or cervix were counted for wild type (black) or fat-1 (white) mice. Asterisks indicate those comparisons (wild type vs. fat-1 mice) with statistical significance (p < 0.05).
Mentions: Of the leukocytes that may contribute to recruitment and amplification of inflammatory reactions, macrophages are the predominant immune cell subtype residing in the uterus26. Macrophages produce a variety of factors, including prostaglandins and cytokines, that regulate uterine contractile activity2527. We therefore studied the macrophages infiltrating the myometria and cervices of fat-1 and wild type mice using immunohistochemical detection of F4/80-immunoreactive cells (Fig. 2A). Infiltration of F4/80-immunoreactive macrophages into the myometrium was observed in both wild type and fat-1 mice exposed to LPS (Fig. 2A, left lower two panels). Cervical infiltrating macrophages were also observed in LPS-injected wild type mice (26 ± 5.7 macrophages per 10 microscope fields, n = 3) but were quite infrequent in LPS-injected fat-1 mice (11 ± 2.0 macrophages per 10 microscope fields, n = 3) (right, lower two panels). F4/80 positive macrophages were quantitated and comparisons were made between fat-1 and wild type mice (Fig. 2B). No differences were detected in the number of myometrial infiltrating macrophages in LPS-injected fat-1 and wild type mice. In contrast, the number of cervical infiltrating macrophages in fat-1 mice was significantly lower than that in the wild type mice.

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