The role of IP-10 and its receptor CXCR3 in early pregnancy

Jiang, Ying; Huang, Feng‐Ying; Chai, Xiaoshan; Yuan, Weiying; Ding, Hui; Wu, Xianqing

doi:10.1016/j.molimm.2021.09.013

Cited by 13 publications

(11 citation statements)

References 36 publications

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“…CXCL10 was highly upregulated in both astrocytes and microglia of all brain regions in astrocytic YY1 cKO mice as well as YY1‐knockdown astrocytic cultures (Figure 10), suggesting that astrocytes are responsible for the inflammatory phenotype in the brain (Mockenhaupt et al, 2021), at least in part by YY1 deficiency in astrocytes. CXCL10 upregulation is linked to neurodegenerative diseases (Xia et al, 2000) and induces neuronal injury by dysregulating mitochondrial function (Sui et al, 2006) and promoting a proinflammatory environment (Jiang, Huang, et al, 2021). TNF‐α was also increased in microglia in the Alzheimer's disease model (Shippy et al, 2022), supporting the preventive role of astrocytic YY1 in neuroinflammation.…”

Section: Discussionmentioning

confidence: 99%

Astrocytic Yin Yang 1 is critical for murine brain development and protection against apoptosis, oxidative stress, and inflammation

Pajarillo

Nyarko-Danquah

Digman

et al. 2022

Glia

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The transcription factor Yin Yang 1 (YY1) is ubiquitously expressed in mammalian cells, regulating the expression of a variety of genes involved in proliferation, differentiation, and apoptosis in a context-dependent manner. While it is well-established that global YY1 knockout (KO) leads to embryonic death in mice and that YY1 deletion in neurons or oligodendrocytes induces impaired brain function, the role of astrocytic YY1 in the brain remains unknown. We investigated the role of astrocytic YY1 in the brain using a glial fibrillary acidic protein (GFAP)-specific YY1 conditional KO (YY1 cKO) mouse model to delete astrocytic YY1. Astrocytic YY1 cKO mice were tested for behavioral phenotypes, such as locomotor activity, coordination, and cognition, followed by an assessment of relevant biological pathways using RNA-sequencing analysis, immunoblotting, and immunohistochemistry in the cortex, midbrain, and cerebellum. YY1 cKO mice showed abnormal phenotypes, movement deficits, and cognitive dysfunction. At the molecular level, astrocytic YY1 deletion altered the expression of genes associated with proliferation and differentiation, p53/caspase apoptotic pathways, oxidative stress response, and inflammatory signaling including NF-κB, STAT, and IRF in all regions. Astrocytic YY1 deletion significantly increased the expression of GFAP as astrocytic activation and Iba1 as microglial activation, indicating astrocytic YY1 deletion activated microglia as well. Accordingly, multiple inflammatory cytokines and chemokines including TNF-α and CXCL10 were elevated. Combined, these novel findings suggest that astrocytic YY1 is a critical transcription factor for normal brain development and locomotor activity, motor coordination, and cognition. Astrocytic YY1 is also essential in preventing pathological oxidative stress, apoptosis, and inflammation.

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Section: Discussionmentioning

confidence: 99%

Astrocytic Yin Yang 1 is critical for murine brain development and protection against apoptosis, oxidative stress, and inflammation

Pajarillo

Nyarko-Danquah

Digman

et al. 2022

Glia

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“…This phenomenon contributes to the construction of the local proinflammatory environment of endometrial tissue and facilitates tissue remodeling and angiogenesis. Such processes can enhance the implantation of embryos based on the association with the endometrial microenvironment during the first trimester ( Gervasi et al, 2012 ; Jia and Li, 2020 ; Jiang et al, 2021 ). MCP-1, RANTES might be predictive factors for diabetic pregnancy in early pregnancy development, which levels associated with perinatal outcome ( Wender-Ozegowska et al, 2008 ).…”

Section: Discussionmentioning

confidence: 99%

Associations of circulation levels of cytokines with birthweight, preterm birth, spontaneous miscarriages, and stillbirth: A Mendelian randomization analysis

et al. 2023

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Background: The association between immune imbalances and adverse pregnancy outcomes has been extensive investigated by observational studies, but remain unclear. Thus, this study aimed to establish the causality of the circulation levels of cytokines on adverse pregnancy outcomes, such as offspring’s birthweight (BW), preterm birth (PTB), spontaneous miscarriage (SM), and stillbirth (SB).Methods: Two-sample Mendelian randomization (MR) analysis was employed to investigate potential causal relations between 41 cytokines and pregnancy outcomes on the basis of previously published GWAS datasets. Multivariable MR (MVMR) analysis was implemented to investigate the effect of the composition of cytokine networks on the pregnancy outcomes. Potential risk factors were further estimated to explore the potential mediators.Results: Genetic correlation analysis based on large GWAS data sources revealed that genetically predicted MIP1b (β = −0.027, S.E. = 0.010, p = 0.009) and MCSF (β = −0.024, S.E. = 0.011, p = 0.029) were associated with reduced offspring’s BW, MCP1 (OR: 0.90, 95% CI: 0.83–0.97, p = 0.007) was associated with reduced SM risk, SCF (β = −0.014, S.E. = 0.005, p = 0.012) associated with decreased number of SB in MVMR. The univariable MR showed that GROa (OR: 0.92, 95% CI: 0.87–0.97, p = 0.004) was associated with decreased PTB risk. Except for the MCSF-BW association, all above associations surpassed the Bonferroni corrected threshold. The MVMR results revealed that MIF, SDF1a, MIP1b, MCSF and IP10 composed cytokine networks, associated with offspring’s BW. Risk factors analysis indicated that the above causal associations might be mediated by smoking behaviors.Conclusion: These findings suggest the causal associations of several cytokines with adverse pregnancy outcomes, which were potentially mediated by smoking and obesity. Some of the results did not been corrected through multiple tests and larger samples verification is required in further studies.

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“…Interestingly, our lab and others have identi ed multiple cytokines, -IL-1β, IL-8, MIP-1β, TNFα, VEGFa, and IFNγ, that are consistently differentially present in seminal plasma, ULF, blood samples, and vaginal uid which may impact the reproductive environment and subsequent pregnancy outcome (17,(24)(25)(26)(27)33). In ammation early in gestation has been reported to be important during the establishment of pregnancy and embryonic development in mice (31,34), humans (34,35), sheep (36), and with the growing body of literature most likely cattle. Nonetheless, more research needs to be conducted to understand the importance and timing of in ammation during early embryonic development and the establishment of gestation.…”

Section: Discussionmentioning

confidence: 99%

The Impacts of Protein Supplementation and Semen Exposure on Uterine Cytokines in Beef Heifers

McLean,

Brandt,

Ault-Seay

et al. 2023

Preprint

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Reproductive efficiency is largely impacted during heifer development which generally requires nutrient supplementation for proper maturation. Nutritional status can also influence inflammation within the reproductive tract. Therefore, we hypothesized that cytokine concentrations in uterine luminal fluid (ULF) will be impacted by protein supplementation following artificial insemination (AI). Commercial heifers (n = 60) were utilized to determine the effects of protein supplementation and AI on cytokine concentrations in ULF. Heifers were randomly assigned to one of three supplemental treatments: 1) CON (10% crude protein [CP]), 2) P20 (20% CP), and 3) P40 (40% CP). All heifers underwent estrus synchronization and ULF was collected 14 d after insemination. Cytokine profiles were constructed in MetaboAnalyst 5.0 and R Studio was used for individual cytokine analyses. Control heifers had increased (P = 0.05) MIP-1β concentrations (148.7 ± 123.9pg) over P20 heifers (42.3 ± 123.9pg) and P40 heifers (75.5 ± 123.9pg) were intermediate. Semen exposure (1877 ± 550pg) tended (P = 0.06) to increase concentrations of IP-10 compared with heifers who were not inseminated (1556 ± 550pg). In conclusion, protein supplementation and exposure to semen had a limited impact on the cytokine profiles and individual cytokine concentrations in the ULF of heifers following AI but did identify three cytokines providing potential targets important in early gestation.

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The role of IP-10 and its receptor CXCR3 in early pregnancy

Cited by 13 publications

References 36 publications

Astrocytic Yin Yang 1 is critical for murine brain development and protection against apoptosis, oxidative stress, and inflammation

Astrocytic Yin Yang 1 is critical for murine brain development and protection against apoptosis, oxidative stress, and inflammation

Associations of circulation levels of cytokines with birthweight, preterm birth, spontaneous miscarriages, and stillbirth: A Mendelian randomization analysis

The Impacts of Protein Supplementation and Semen Exposure on Uterine Cytokines in Beef Heifers

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