REVIEW: Transcription Factor KLF2 and Its Role in the Regulation of Inflammatory Processes

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K. T. Turpaev^a

Center for Theoretical Problems of Physicochemical Pharmacology, Russian Academy of Sciences, 119991 Moscow, Russia

Received May 11, 2019; Revised August 2, 2019; Accepted October 7, 2019

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KLF2 is a member of the Krüppel-like transcription factor family of proteins containing highly conserved DNA-binding zinc finger domains. KLF2 participates in the differentiation and regulation of the functional activity of monocytes, T lymphocytes, adipocytes, and vascular endothelial cells. The activity of KLF2 is controlled by several regulatory systems, including the MEKK2,3/MEK5/ERK5/MEF2 MAP kinase cascade, Rho family G-proteins, histone acetyltransferases CBP and p300, and histone deacetylases HDAC4 and HDAC5. Activation of KLF2 in endothelial cells induces eNOS expression and provides vasodilatory effect. Many KLF2-dependent genes participate in the suppression of blood coagulation and aggregation of T cells and macrophages with the vascular endothelium, thereby preventing atherosclerosis progression. KLF2 can have a dual effect on the gene transcription. Thus, it induces expression of multiple genes, but suppresses transcription of NF-κB-dependent genes. Transcription factors KLF2 and NF-κB are reciprocal antagonists. KLF2 inhibits induction of NF-κB-dependent genes, whereas NF-κB downregulates KLF2 expression. KLF2-mediated inhibition of NF-κB signaling leads to the suppression of cell response to the pro-inflammatory cytokines IL-1β and TNFα and results in the attenuation of inflammatory processes.

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KEY WORDS: KLF2, zinc fingers, regulation of transcription, pro-inflammatory cytokines, endothelium

DOI: 10.1134/S0006297920010058

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