Accepted Manuscript Title: The effect of progesterone on genes involved in preterm labor Author: Hitomi Okabe Shintaro Makino Kiyoko Kato Kikumi Matsuoka Hiroyuki Seki Satoru Takeda PII: DOI: Reference:
S0165-0378(14)00038-2 http://dx.doi.org/doi:10.1016/j.jri.2014.03.008 JRI 2254
To appear in:
Journal
Received date: Revised date: Accepted date:
30-10-2013 19-3-2014 26-3-2014
of
Reproductive
Immunology
Please cite this article as: Okabe, H., Makino, S., Kato, K., Matsuoka, K., Seki, H., Takeda, S.,The effect of progesterone on genes involved in preterm labor, Journal of Reproductive Immunology (2014), http://dx.doi.org/10.1016/j.jri.2014.03.008 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
*Manuscript
The effect of progesterone on genes involved in preterm labor
Hitomi Okabea, Shintaro Makinoa*, Kiyoko Katoa, Kikumi Matsuokab, Hiroyuki Sekib,
ip t
Satoru Takedaa 5
of Obstetrics and Gynecology, Juntendo University Faculty of Medicine,
cr
aDepartment
bCenter
us
Tokyo, Japan
for Maternal, Fetal and Neonatal Medicine, Saitama Medical Center, Saitama,
an
Japan
M
10
*Corresponding author: Shintaro Makino M.D., PhD.
ed
Department of Obstetrics and Gynecology, Juntendo University Faculty of Medicine,
ce pt
2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan Tel: +81-3-5802-1100; Fax: +81-3-5689-7460; E-mail address: [email protected] 15
Ac
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65
1 Page 1 of 40
Abstract The decidua is known to be a major source of intrauterine PGF2α during late gestation
ip t
and labor, and inflammatory cytokines, including IL-1β, IL-6, and IL-8, are elevated in spontaneous preterm deliveries. In the present study, to elucidate how progesterone blocks the pathways associated with preterm birth, we determined the effects of P4 on
cr
20
us
the expression of PTGS-2 and PTGFR mRNA in human decidua fibroblast cells, as well
an
as the genes, using microarray analysis. Senescence was induced in primary cultured
M
human decidual cells treated with IL-1β. The IL-1β treatment implicated by microarray analysis increased gene expression levels of PTGS-2, PTGFR, NFκ-B p65, IL-17, and IL-8. In contrast, P4 + IL-1β decreased the expression levels of all of these genes in
ed
25
ce pt
comparison to treatment with IL-1β alone (p
S0165-0378(14)00038-2 http://dx.doi.org/doi:10.1016/j.jri.2014.03.008 JRI 2254
To appear in:
Journal
Received date: Revised date: Accepted date:
30-10-2013 19-3-2014 26-3-2014
of
Reproductive
Immunology
Please cite this article as: Okabe, H., Makino, S., Kato, K., Matsuoka, K., Seki, H., Takeda, S.,The effect of progesterone on genes involved in preterm labor, Journal of Reproductive Immunology (2014), http://dx.doi.org/10.1016/j.jri.2014.03.008 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
*Manuscript
The effect of progesterone on genes involved in preterm labor
Hitomi Okabea, Shintaro Makinoa*, Kiyoko Katoa, Kikumi Matsuokab, Hiroyuki Sekib,
ip t
Satoru Takedaa 5
of Obstetrics and Gynecology, Juntendo University Faculty of Medicine,
cr
aDepartment
bCenter
us
Tokyo, Japan
for Maternal, Fetal and Neonatal Medicine, Saitama Medical Center, Saitama,
an
Japan
M
10
*Corresponding author: Shintaro Makino M.D., PhD.
ed
Department of Obstetrics and Gynecology, Juntendo University Faculty of Medicine,
ce pt
2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan Tel: +81-3-5802-1100; Fax: +81-3-5689-7460; E-mail address: [email protected] 15
Ac
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65
1 Page 1 of 40
Abstract The decidua is known to be a major source of intrauterine PGF2α during late gestation
ip t
and labor, and inflammatory cytokines, including IL-1β, IL-6, and IL-8, are elevated in spontaneous preterm deliveries. In the present study, to elucidate how progesterone blocks the pathways associated with preterm birth, we determined the effects of P4 on
cr
20
us
the expression of PTGS-2 and PTGFR mRNA in human decidua fibroblast cells, as well
an
as the genes, using microarray analysis. Senescence was induced in primary cultured
M
human decidual cells treated with IL-1β. The IL-1β treatment implicated by microarray analysis increased gene expression levels of PTGS-2, PTGFR, NFκ-B p65, IL-17, and IL-8. In contrast, P4 + IL-1β decreased the expression levels of all of these genes in
ed
25
ce pt
comparison to treatment with IL-1β alone (p
