Map3k8, also known as Cot/Tpl2, is a serine/threonine kinase that plays a key role in activating the MKK1/2-ERK1/2 MAPK pathway downstream from various receptors like interleukin-1R, tumor necrosis factor-αR, NOD-2R, adiponectinR, and Toll-like receptors [2]. It is involved in innate and adaptive immunity, influencing inflammatory processes by modulating functions of different cell types [2].

In various disease models, Map3k8 shows distinct roles. In ApoE-/-mice, Map3k8 deficiency led to smaller numbers of certain monocyte subsets, increased monocyte apoptosis, and reduced atherosclerotic plaque cellular infiltration and lipid content, suggesting its role in atherogenesis [2]. In lipopolysaccharide-induced emergency granulopoiesis, Map3k8-/-mice had decreased production of granulocyte colony-stimulating factor (G-CSF) and impaired neutrophil precursor proliferation [3]. In the context of pulmonary fibrosis, Map3k8 mRNA levels were decreased in IPF patients and bleomycin-induced fibrotic mice. Ubiquitous or macrophage-specific genetic deletion of Map3k8 exacerbated the disease, indicating its role in regulating pulmonary inflammation and fibrosis [1].

In conclusion, Map3k8 is a crucial regulator in multiple biological processes related to immunity and inflammation. Gene knockout mouse models have revealed its significance in diseases such as atherosclerosis, emergency granulopoiesis, and pulmonary fibrosis. Understanding Map3k8 function provides insights into disease mechanisms and potential therapeutic targets for these conditions.

References:

1. Zannikou, Markella, Barbayianni, Ilianna, Fanidis, Dionysios, Kaffe, Eleanna, Aidinis, Vassilis. 2020. MAP3K8 Regulates Cox-2-Mediated Prostaglandin E2 Production in the Lung and Suppresses Pulmonary Inflammation and Fibrosis. In Journal of immunology (Baltimore, Md. : 1950), 206, 607-620. doi:10.4049/jimmunol.2000862. https://pubmed.ncbi.nlm.nih.gov/33443087/

2. Sanz-Garcia, Carlos, Sánchez, Ángela, Contreras-Jurado, Constanza, Aranda, Ana, Alemany, Susana. 2016. Map3k8 Modulates Monocyte State and Atherogenesis in ApoE-/- Mice. In Arteriosclerosis, thrombosis, and vascular biology, 37, 237-246. doi:10.1161/ATVBAHA.116.308528. https://pubmed.ncbi.nlm.nih.gov/27856455/

3. Sánchez, Ángela, Relaño, Carlos, Carrasco, Araceli, Aranda, Ana, Alemany, Susana. 2017. Map3k8 controls granulocyte colony-stimulating factor production and neutrophil precursor proliferation in lipopolysaccharide-induced emergency granulopoiesis. In Scientific reports, 7, 5010. doi:10.1038/s41598-017-04538-3. https://pubmed.ncbi.nlm.nih.gov/28694430/