KLF2 in Regulation of NF-κB-Mediated Immune Cell Function and Inflammation

Abstract

KLF2 (Kruppel-like factor 2) is a member of the zinc finger transcription factor family, which critically regulates embryonic lung development, function of endothelial cells and maintenance of quiescence in T-cells and monocytes. It is expressed in naïve T-cells and monocytes, however its level of expression decreases during activation and differentiation. KLF2 also plays critical regulatory role in various inflammatory diseases and their pathogenesis. Nuclear factor-kappaB (NF-κB) is an important inducer of inflammation and the inflammation is mediated through the transcription of several proinflammatory cytokines, chemokines and adhesion molecules. So, both transcriptional factors KLF2 and NF-κB are being associated with the similar cellular functions and their maintenance. It was shown that KLF2 regulates most of the NF-κB-mediated activities. In this review, we focused on emphasizing the involvement of KLF2 in health and disease states and how they interact with transcriptional master regulator NF-κB.

Iron Deprivation in Human T Cells Induces Nonproliferating Accessory Helper Cells

“…Next, we analyzed the expression levels of a regulator of T cell quiescence, KLF2 (28). Results presented in Fig.…”

Prevention of Hepatocellular Carcinoma by Statins: Clinical Evidence and Plausible Mechanisms

“…67 The Rho pathway and myocyte enhancer factor-2 binding site of KLF-2 promoter are implicated for statin-induced KLF-2 expression, and KLF-2 plays as a novel nuclear mediator of statin effects in endothelial cells. 68,69 KLF-2 also inhibits NF-κB transcriptional activity and acts as a regulator of inflammation and fibrosis. 69 Upregulation of KLF-2 expression in hepatic endothelial cells by statin treatment limits fibrogenic HSC activation, reduces hepatic oxidative stress, and attenuates the portal blood flow and hepatic vascular resistance, thereby improving endothelial function and preventing hepatic fibrosis.…”

Anti-Neuroinflammatory Effect of Alantolactone through the Suppression of the NF-κB and MAPK Signaling Pathways

“…Further evaluation using a middle cerebral artery occlusion and reperfusion (MCAO/R) rat model supported the conclusion that Ala could (1) alleviate cerebral ischemia-reperfusion injury; (2) reduce neurological deficits, cerebral infarct volume, and brain edema; and (3) attenuate the apoptosis and necrosis of neurons. In sum, Ala demonstrates anti-neuroinflammatory properties that contribute to the amelioration of CNS damage, and it could be a promising candidate for future applications in CNS injury treatment.be found that two signaling pathways stand out as being strongly associated with the production of proinflammatory factors: Nuclear factor kappa light-chain enhancer of activated B cells (NF-κB) [10] and mitogen-activated protein kinase (MAPK) [11].Because it is responsible for the transcription of several proinflammatory cytokines, chemokines, and adhesion molecules, the NF-κB signaling pathway plays a crucial role in many diseases that involve dysregulation of the inflammatory response [12,13]. The NF-κB signaling pathway consists of a series of intracellular secondary reactions [14,15].…”

“…Because it is responsible for the transcription of several proinflammatory cytokines, chemokines, and adhesion molecules, the NF-κB signaling pathway plays a crucial role in many diseases that involve dysregulation of the inflammatory response [12,13]. The NF-κB signaling pathway consists of a series of intracellular secondary reactions [14,15].…”