2-Cyclopropylimino-3-methyl-1,3-thiazoline hydrochloride alters lipopolysaccharide-induced proinflammatory cytokines and neuronal morphology in mouse fetal brain.

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.