Il1a-KO Mouse

Il1a, also known as interleukin 1 alpha, is a pro-inflammatory cytokine. It is involved in various immune and inflammatory responses, and is associated with pathways such as the NF-κB signaling pathway which controls much of the senescence-associated secretory phenotype (SASP) [1]. IL1A is crucial in the body's response to inflammation, cell senescence, and in some cases, disease development. Genetic models, like gene knockout in mice, can help to understand its functions better.

In mouse models, rapamycin, which suppresses the mammalian TORC1 complex, selectively blunts the pro-inflammatory phenotype of senescent cells by reducing IL1A translation. This reduction in IL1A diminishes NF-κB transcriptional activity and the SASP, and rapamycin suppresses the ability of senescent fibroblasts to stimulate prostate tumour growth in mice [1]. In glaucoma-relevant models, while intravitreal injection of IL1A alone does not cause retinal ganglion cell (RGC) death, it enhances TNF-induced RGC death in a SARM1-dependent manner [2]. In lung ischemia reperfusion injury (IRI) mouse models, both the mRNA and protein expression levels of IL1A are significantly elevated in the IRI group compared to the control group, indicating its potential role as a biomarker for lung IRI following lung transplantation [3].

In summary, Il1a is an important pro-inflammatory cytokine involved in multiple biological processes. Through model-based research, especially in KO mouse models, its role in inflammation-related diseases such as cancer, glaucoma, and lung IRI has been revealed. Understanding Il1a helps to better comprehend the mechanisms of these diseases and may provide potential targets for treatment.

References:

1. Laberge, Remi-Martin, Sun, Yu, Orjalo, Arturo V, Nelson, Peter S, Campisi, Judith. 2015. MTOR regulates the pro-tumorigenic senescence-associated secretory phenotype by promoting IL1A translation. In Nature cell biology, 17, 1049-61. doi:10.1038/ncb3195. https://pubmed.ncbi.nlm.nih.gov/26147250/

2. Andersh, Katherine M, MacLean, Michael, Howell, Gareth R, Libby, Richard T. 2024. IL1A enhances TNF-induced retinal ganglion cell death. In bioRxiv : the preprint server for biology, , . doi:10.1101/2024.05.28.596328. https://pubmed.ncbi.nlm.nih.gov/38854045/

3. Zhang, Nan, Zhang, Qingqing, Zhang, Zhiyuan, Jiang, Ping, Wen, Zongmei. 2024. IRF1 and IL1A associated with PANoptosis serve as potential immune signatures for lung ischemia reperfusion injury following lung transplantation. In International immunopharmacology, 139, 112739. doi:10.1016/j.intimp.2024.112739. https://pubmed.ncbi.nlm.nih.gov/39074415/