title: 2-Cyclopropylimino-3-methyl-1,3-thiazoline hydrochloride alters lipopolysaccharide-induced proinflammatory cytokines and neuronal morphology in mouse fetal brain.
abstract: It is well documented that a maternal immune response to infection during pregnancy can cause neurodevelopmental damage. We demonstrate in our current study that maternally administered 2-cyclopropylimino-3-methyl-1,3-thiazoline hydrochloride (KHG26377), a novel thiazole derivative, prevents fetal malformations and neurodevelopmental deficits in offspring by blocking lipopolysaccharide (LPS)-induced inflammation. Administration of KHG26377 effectively regulated LPS-induced inflammatory markers and mediators such as soluble intercellular adhesion molecule-1, se-Selectin, macrophage chemoattractant protein-1, and cytokine-induced neutrophil chemoattractant-1 in the maternal serum. Furthermore, maternally administered KHG26377 showed an inhibitory effect on the LPS-induced developmental toxicity by selectively suppressing the TNF-α level in maternal serum, amniotic fluid, placenta, fetal liver, and fetal brain as well as by suppression of LPS-induced nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2), and myelin basic protein (MBP) levels in the fetal brain. In addition, pretreatment of neuronal cells with KHG26377 effectively reestablished the cell body morphology and microtubule-associated protein 2 (MAP2) staining compared to the LPS-treated group in cortex primary neuronal cultures. Although the clinical relevance of our findings remains to be determined, our results provide novel insights into KHG26377 as a possible therapeutic agent to protect fetuses against various inflammatory responses.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul 138-736, South Korea.
authors.forename: Eun-A
authors.initials: EA
authors.lastname: Kim
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul 138-736, South Korea.
authors.forename: Chang Hun
authors.initials: CH
authors.lastname: Cho
authors.affiliation: Department of Biomedical Science and Research Institute for Bioscience and Biotechnology, Hallym University, Chunchon 200-702, South Korea.
authors.forename: Soo Young
authors.initials: SY
authors.lastname: Choi
authors.affiliation: Department of Molecular Cell Biology, Center for Molecular Medicine, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746, South Korea.
authors.forename: Jee-Yin
authors.initials: JY
authors.lastname: Ahn
authors.affiliation: Department of Biomedical Laboratory Science, Konyang University, 158, Gwangeodong-ro, Seo-gu, Daejeon 302-832, South Korea. Electronic address: sjyang@konyang.ac.kr.
authors.forename: Seung-Ju
authors.initials: SJ
authors.lastname: Yang
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul 138-736, South Korea. Electronic address: swcho@amc.seoul.kr.
authors.forename: Sung-Woo
authors.initials: SW
authors.lastname: Cho
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D048430:Cell Shape / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D005333:Fetus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011247:Pregnancy; D013844:Thiazoles / Q000494:pharmacology*
chemical_list: C550808:2-cyclopropylimino-3-methyl-1,3-thiazoline hydrochloride; D016207:Cytokines; D008070:Lipopolysaccharides; D008869:Microtubule-Associated Proteins; D013844:Thiazoles
keywords: Neuroinflammation; Neuronal injury; Neuronal morphology; Preterm birth; Thiazole derivative