Inflammation in preterm birth: Novel mechanism of preterm birth associated with innate and acquired immunity

Negishi, Yasuyuki; Shima, Yoshio; Katô, Masahiko; Ichikawa, Tomoko; Ino, Hajime; Horii, Yumi; Suzuki, Shunji; Morita, Rimpei

doi:10.1016/j.jri.2022.103748

Cited by 10 publications

(10 citation statements)

References 122 publications

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“…It can therefore be suggested that Sr or Mo levels rise when some kind of oxidative damage exists, and this elevation attempts in some way to restore the balance between the organism's defence and its oxidative damage and reduce the risk of SPTB. Moreover, inflammation is thought to be another potential mechanism for PTB (66,67) . A large number of studies have found that Sr could suppress inflammation (68,69) .…”

Section: Discussionmentioning

confidence: 99%

Inverse association between maternal serum concentrations of trace elements and risk of spontaneous preterm birth: a nested case–control study in China

Li,

Yu,

Liu

et al. 2024

Br J Nutr

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Few studies have evaluated the joint effect of trace elements on spontaneous preterm birth (SPTB).This study aimed to examine the relationships between the individual or mixed maternal serum concentrations of iron (Fe), copper (Cu), zinc (Zn), selenium (Se), strontium (Sr) and molybdenum (Mo) during pregnancy, and risk of SPTB. Inductively coupled plasma mass spectrometry was employed to determine maternal serum concentrations of the six trace elements in 192 cases with SPTB and 282 controls with full-term delivery. Multivariate logistic regression, weighted quantile sum regression (WQSR) and Bayesian kernel machine regression (BKMR) were used to evaluate the individual and joint effects of trace elements on SPTB. The median concentrations of Sr and Mo were significantly higher in controls than in SPTB group (P < 0.05). In multivariate logistic regression analysis, compared with the lowest quartile levels of individual trace elements, the third- and fourth-quartile Sr or Mo concentrations were significantly associated with reduced risk of SPTB with adjusted odds ratios (aORs) of 0.432 (95% confidence interval (CI): 0.247-0.756), 0.386 (95% CI: 0.213-0.701), 0.512 (95% CI:0.297-0.883), and 0.559 (95% CI: 0.321-0.972), respectively. WQSR revealed the inverse combined effect of the trace elements mixture on SPTB (aOR: 0.368, 95%CI: 0.228-0.593). BKMR analysis confirmed the overall mixture of the trace elements was inversely associated with the risk of SPTB, and the independent effect of Sr and Mo was significant. Our findings suggest that the risk of SPTB decreased with concentrations of the six trace elements, with Sr and Mo being the major contributors.

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Section: Discussionmentioning

confidence: 99%

Inverse association between maternal serum concentrations of trace elements and risk of spontaneous preterm birth: a nested case–control study in China

Li,

Yu,

Liu

et al. 2024

Br J Nutr

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“…The process of initiating delivery in preterm labor is similar to that of term labor, albeit occurring earlier than expected ( 30 ). However, the precise mechanisms underlying the initiation of labor are not yet fully understood ( 31 , 32 ). Recent studies suggest that the initiation of labor involves an inflammatory response ( 31 , 32 ).…”

Section: Discussionmentioning

confidence: 99%

“…However, the precise mechanisms underlying the initiation of labor are not yet fully understood ( 31 , 32 ). Recent studies suggest that the initiation of labor involves an inflammatory response ( 31 , 32 ).…”

Section: Discussionmentioning

confidence: 99%

“…Inflammatory activation plays a central and primary role in the processes of parturition, characterized by the accelerated influx of inflammatory leukocytes and synthesis and release of cytokines in the serum and gestational tissues ( 31 ). In our study, we assessed the expression levels of cytokines in the serum of TNL and TL pregnant women.…”

Section: Discussionmentioning

confidence: 99%

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Elevated expression of Toll-like receptor 4 and cytokines in both serum and myometrium at term may serve as promising biomarkers for uterine activation preceding labor

Chen,

Li,

et al. 2023

Front. Endocrinol.

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ObjectiveIncreased inflammation and cytokine levels are considered risk factors and promoters of preterm birth (PTB). However, the regulatory mechanism of pregnancy-related inflammation remains unclear. Toll-like receptor 4 (TLR4) plays a critical role in inflammatory responses in various diseases. Therefore, our study aimed to investigate whether TLR4 is involved in the inflammatory responses during uterine activation for labor, with the goal of identifying potential biomarkers for uterine activation at term.Materials and methodsWe used flow cytometry to detect TLR4 expression on CD14+ maternal blood monocytes in the first, second, and third trimesters. ELISA was employed to measure TLR4 and cytokines levels in the maternal serum of term non-labor (TNL), term labor (TL) women and LPS induced preterm labor and PBS injected controls. TLR4siRNA was transfected into the human myometrial smooth muscle cells (HMSMCs), which were subsequently treated with IL-1β. The mRNA and protein levels of TLR4, uterine contraction-related protein connexin 43 (CX43), oxytocin receptor (OTR), MAPK/NF-κB signaling pathway, and cytokines were analyzed using qRT-PCR, western blotting, and immunohistochemistry.ResultsThe study revealed TLR4 expression on CD14+ maternal blood monocytes was higher in the third trimester group compared to the first and second trimester groups (p<0.001). Maternal serum concentrations of TLR4 and cytokines were significantly higher in the TL group than the TNL group (p<0.001). TLR4, OTR, CX43, activated MAPK/NF-κB expression, and cytokines levels were upregulated in TL group, and similarly significantly higher in the LPS-induced preterm group than in the control group. Using the HMSMCs we demonstrated that TLR4siRNA transfection suppressed contractility. Interfering with TLR4 expression reduced the expression of OTR, CX43, cytokines, and MAPK/NF-κB activation. There was a significant positive relationship between TLR4 expression and the inflammatory status in the myometrium. ROC analysis indicated that TLR4 and cytokines may serve as potential biomarkers for predicting uterine activation for labor.ConclusionOur data suggest that TLR4 and cytokines can act as stimulators of uterine activation for labor at term. Furthermore, the MAPK/NF-κB pathway appears to be one of the potential signaling pathways mediating TLR4’s regulation of parturition initiation.

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“…This cytokine has been associated with impairments in the blood – brain barrier and the infiltration of neutrophils into the brain parenchyma [ 54 ]. The IL-1 family comprises 11 members, including IL-1α and IL-1β; shares a receptor; and exhibits similar functions, with IL-1β being tightly regulated through macrophage inflammasomes [ 55 , 56 ]. Particularly, IL-1β, TNF-α, and IL-6 can trigger the expression of proinflammatory genes in astrocytes, contributing to neuroinflammation and neurodegeneration [ 50 ].…”

Section: Discussionmentioning

confidence: 99%

Potential Inflammatory Biomarkers for Major Depressive Disorder Related to Suicidal Behaviors: A Systematic Review

Kim,

Shin,

Chang

2023

IJMS

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Major depressive disorder (MDD) is a highly prevalent psychiatric condition affecting an estimated 280 million individuals globally. Despite the occurrence of suicidal behaviors across various psychiatric conditions, MDD is distinctly associated with the highest risk of suicide attempts and death within this population. In this study, we focused on MDD to identify potential inflammatory biomarkers associated with suicidal risk, given the relationship between depressive states and suicidal ideation. Articles published before June 2023 were searched in PubMed, Embase, Web of Science, and the Cochrane Library to identify all relevant studies reporting blood inflammatory biomarkers in patients with MDD with suicide-related behaviors. Of 571 articles, 24 were included in this study. Overall, 43 significant biomarkers associated with MDD and suicide-related behaviors were identified. Our study provided compelling evidence of significant alterations in peripheral inflammatory factors in MDD patients with suicide-related behaviors, demonstrating the potential roles of interleukin (IL)-1β, IL-6, C-reactive protein, C-C motif chemokine ligand 2, and tumor necrosis factor-α as biomarkers. These findings underscore the intricate relationship between the inflammatory processes of these biomarkers and their interactions in MDD with suicidal risk.

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Inflammation in preterm birth: Novel mechanism of preterm birth associated with innate and acquired immunity

Cited by 10 publications

References 122 publications

Inverse association between maternal serum concentrations of trace elements and risk of spontaneous preterm birth: a nested case–control study in China

Inverse association between maternal serum concentrations of trace elements and risk of spontaneous preterm birth: a nested case–control study in China

Elevated expression of Toll-like receptor 4 and cytokines in both serum and myometrium at term may serve as promising biomarkers for uterine activation preceding labor

Potential Inflammatory Biomarkers for Major Depressive Disorder Related to Suicidal Behaviors: A Systematic Review

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