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Involvement of p38 MAP kinase in lipopolysaccharide-induced production of pro- and anti-inflammatory cytokines and prostaglandin E(2) in human choriodecidua.
J Reprod Immunol 2007; 75(2):82-90JR

Abstract

Chorioamnionitis is implicated in the pathogenesis of preterm delivery. However, the detailed mechanisms by which infection induces preterm labor are not well understood. This study has assessed the involvement of mitogen-activated protein (MAP) kinases in lipopolysaccharide (LPS)-induced pro- and anti-inflammatory cytokine and prostaglandin (PG) production in human choriodecidua. Samples of choriodecidua were collected before the onset of labor from women undergoing elective cesarean sections at term for breech presentation, previous cesarean delivery or cephalopelvic disproportion. Concentrations of TNFalpha, IL-10, PGE(2) and PGF(2)alpha in culture supernatants were measured by ELISA. Expression of COX-2 protein was analyzed by Western blotting. In human choriodecidual explants, LPS induced TNFalpha and IL-10 production in a dose- and time-dependent manner. LPS also up-regulated COX-2 expression and PG synthesis. Phosphorylations of extracellular signal-regulated kinase (ERK) 1/2, p38 MAPK, and c-Jun N-terminal kinases (JNK) were also confirmed by Western blotting. Furthermore, the effect of MAPK inhibitors was examined on LPS-induced pro- and anti-inflammatory cytokines and PG synthesis. Among the MAPK inhibitors examined, the p38 MAPK inhibitor, SB202190, significantly suppressed LPS-induced cytokine and PG production. SB202190 most profoundly suppressed the TNFalpha to IL-10 ratio, demonstrating that p38 MAPK inhibitor reduced predominantly TNFalpha other than IL-10 production. Phospho-p38 MAPK immunostaining was intense in extravillous trophoblast cells. The p38 MAPK seems to be most involved in signaling mechanisms when infection and inflammation cause preterm labor through PG synthesis. Novel therapeutic modalities targeting p38 MAPK may prevent to arrest preterm labor.

Authors+Show Affiliations

Department of Obstetrics and Gynecology, Tottori University School of Medicine, 36-1 Nishimachi, Yonago, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

17617469

Citation

Shoji, Takako, et al. "Involvement of P38 MAP Kinase in Lipopolysaccharide-induced Production of Pro- and Anti-inflammatory Cytokines and Prostaglandin E(2) in Human Choriodecidua." Journal of Reproductive Immunology, vol. 75, no. 2, 2007, pp. 82-90.
Shoji T, Yoshida S, Mitsunari M, et al. Involvement of p38 MAP kinase in lipopolysaccharide-induced production of pro- and anti-inflammatory cytokines and prostaglandin E(2) in human choriodecidua. J Reprod Immunol. 2007;75(2):82-90.
Shoji, T., Yoshida, S., Mitsunari, M., Miyake, N., Tsukihara, S., Iwabe, T., ... Terakawa, N. (2007). Involvement of p38 MAP kinase in lipopolysaccharide-induced production of pro- and anti-inflammatory cytokines and prostaglandin E(2) in human choriodecidua. Journal of Reproductive Immunology, 75(2), pp. 82-90.
Shoji T, et al. Involvement of P38 MAP Kinase in Lipopolysaccharide-induced Production of Pro- and Anti-inflammatory Cytokines and Prostaglandin E(2) in Human Choriodecidua. J Reprod Immunol. 2007;75(2):82-90. PubMed PMID: 17617469.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Involvement of p38 MAP kinase in lipopolysaccharide-induced production of pro- and anti-inflammatory cytokines and prostaglandin E(2) in human choriodecidua. AU - Shoji,Takako, AU - Yoshida,Souichi, AU - Mitsunari,Masahiro, AU - Miyake,Noriko, AU - Tsukihara,Satoru, AU - Iwabe,Tomio, AU - Harada,Tasuku, AU - Terakawa,Naoki, Y1 - 2007/07/06/ PY - 2006/12/13/received PY - 2007/05/14/revised PY - 2007/05/16/accepted PY - 2007/7/10/pubmed PY - 2007/12/13/medline PY - 2007/7/10/entrez SP - 82 EP - 90 JF - Journal of reproductive immunology JO - J. Reprod. Immunol. VL - 75 IS - 2 N2 - Chorioamnionitis is implicated in the pathogenesis of preterm delivery. However, the detailed mechanisms by which infection induces preterm labor are not well understood. This study has assessed the involvement of mitogen-activated protein (MAP) kinases in lipopolysaccharide (LPS)-induced pro- and anti-inflammatory cytokine and prostaglandin (PG) production in human choriodecidua. Samples of choriodecidua were collected before the onset of labor from women undergoing elective cesarean sections at term for breech presentation, previous cesarean delivery or cephalopelvic disproportion. Concentrations of TNFalpha, IL-10, PGE(2) and PGF(2)alpha in culture supernatants were measured by ELISA. Expression of COX-2 protein was analyzed by Western blotting. In human choriodecidual explants, LPS induced TNFalpha and IL-10 production in a dose- and time-dependent manner. LPS also up-regulated COX-2 expression and PG synthesis. Phosphorylations of extracellular signal-regulated kinase (ERK) 1/2, p38 MAPK, and c-Jun N-terminal kinases (JNK) were also confirmed by Western blotting. Furthermore, the effect of MAPK inhibitors was examined on LPS-induced pro- and anti-inflammatory cytokines and PG synthesis. Among the MAPK inhibitors examined, the p38 MAPK inhibitor, SB202190, significantly suppressed LPS-induced cytokine and PG production. SB202190 most profoundly suppressed the TNFalpha to IL-10 ratio, demonstrating that p38 MAPK inhibitor reduced predominantly TNFalpha other than IL-10 production. Phospho-p38 MAPK immunostaining was intense in extravillous trophoblast cells. The p38 MAPK seems to be most involved in signaling mechanisms when infection and inflammation cause preterm labor through PG synthesis. Novel therapeutic modalities targeting p38 MAPK may prevent to arrest preterm labor. SN - 0165-0378 UR - https://www.unboundmedicine.com/medline/citation/17617469/Involvement_of_p38_MAP_kinase_in_lipopolysaccharide_induced_production_of_pro__and_anti_inflammatory_cytokines_and_prostaglandin_E_2__in_human_choriodecidua_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0165-0378(07)00119-2 DB - PRIME DP - Unbound Medicine ER -