Mitogen Kinase Kinase (MKK7) Controls Cytokine Production In Vitro and In Vivo in Mice
AuthorsCaliz, Amada D.; email: firstname.lastname@example.org
Yoo, Hyung-Jin; email: email@example.com
Vertii, Anastassiia; email: firstname.lastname@example.org
Dolan, Ana C.; email: email@example.com
Tournier, Cathy; orcid: 0000-0002-4618-2570; email: firstname.lastname@example.org
Davis, Roger J.; email: email@example.com
Keaney, John F.; email: firstname.lastname@example.org
Kant, Shashi; orcid: 0000-0001-8772-6813; email: email@example.com
MetadataShow full item record
AbstractMitogen kinase kinase 4 (MKK4) and mitogen kinase kinase 7 (MKK7) are members of the MAP2K family that can activate downstream mitogen-activated protein kinases (MAPKs). MKK4 has been implicated in the activation of both c-Jun N-terminal kinase (JNK) and p38 MAPK, while MKK7 has been reported to activate only JNK in response to different stimuli. The stimuli, as well as the cell type determine which MAP2K member will mediate a given response. In various cell types, MKK7 contributes to the activation of downstream MAPKs, JNK, which is known to regulate essential cellular processes, such as cell death, differentiation, stress response, and cytokine secretion. Previous studies have also implicated the role of MKK7 in stress signaling pathways and cytokine production. However, little is known about the degree to which MKK4 and MKK7 contribute to innate immune responses in macrophages or during inflammation in vivo. To address this question and to elucidate the role of MKK4 and MKK7 in macrophage and in vivo, we developed MKK4- and MKK7-deficient mouse models with tamoxifen-inducible Rosa26 CreERT. This study reports that MKK7 is required for JNK activation both in vitro and in vivo. Additionally, we demonstrated that MKK7 in macrophages is necessary for lipopolysaccharide (LPS)-induced cytokine production, M1 polarization, and migration, which appear to be a major contributor to the inflammatory response in vivo. Conversely, MKK4 plays a significant, but minor role in cytokine production in vivo.
CitationInternational Journal of Molecular Sciences, volume 22, issue 17, page e9364
DescriptionFrom MDPI via Jisc Publications Router
History: accepted 2021-08-27, pub-electronic 2021-08-29
Publication status: Published
Funder: National Institutes of Health; Grant(s): HL151626, DK107220,
Funder: American Heart Association; Grant(s): 16SDG29660007
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