1. Tumor Necrosis Factor Alpha-Induced Interleukin-1 Alpha Synthesis and Cell Death Is Increased in Mouse Epithelial Cells Infected With Chlamydia muridarum.
- Author
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Nagarajan, Uma M, Cho, Crescentia, Gyorke, Clare E, Nagarajan, Shanmugam, Ezzell, J Ashley, Brochu, Hayden, Huntress, Ian, Harrell, Erin, and Peng, Xinxia
- Subjects
TUMOR necrosis factors ,EPITHELIAL cells ,CELL death ,CHLAMYDIA infections ,CHLAMYDIA ,RESEARCH ,ANIMAL experimentation ,RESEARCH methodology ,INTERLEUKIN-1 ,MEDICAL cooperation ,EVALUATION research ,COMPARATIVE studies ,MICE - Abstract
Chlamydia trachomatis-genital infection in women can be modeled in mice using Chlamydia muridarum. Using this model, it has been shown that the cytokines tumor necrosis factor (TNF)α and interleukin (IL)-1α lead to irreversible tissue damage in the oviducts. In this study, we investigated the contribution of TNFα on IL-1α synthesis in infected epithelial cells. We show that C muridarum infection enhanced TNFα-induced IL-1α expression and release in a mouse epithelial cell line. In addition to IL-1α, several TNFα-induced inflammatory genes were also highly induced, and infection enhanced TNF-induced cell death. In the mouse model of genital infection, oviducts from mice lacking the TNFα receptor displayed minimal staining for IL-1α compared with wild-type oviducts. Our results suggest TNFα and IL-1α enhance each other's downstream effects resulting in a hyperinflammatory response to chlamydial infection. We propose that biologics targeting TNF-induced IL-1α synthesis could be used to mitigate tissue damage during chlamydial infection. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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