Liver Kinase B1 Suppresses Lipopolysaccharide-induced Nuclear Factor κB (NF-κB) Activation in Macrophages

Abstract

Background: LKB1 is a serine/threonine kinase that is essential in metabolism and tumor suppression. Results: LKB1 interacts with IKK␤ and suppresses NF-B activation in response to LPS. Conclusion: LKB1 inhibits LPS-induced inflammatory responses.Significance: This work reveals a novel mechanism for regulating LPS-induced inflammation.

Stromal Lkb1 deficiency leads to gastrointestinal tumorigenesis involving the IL-11–JAK/STAT3 pathway

“…Recently, several reports have identified increased inflammatory signaling upon Lkb1 loss in different cell and tissue contexts, such as in skeletal muscle (12), macrophages (13), T cells (14), and lung cancer (15), implicating Lkb1 as a suppressor of inflammatory pathways. In PJS patients and in Lkb1 +/-mice, inhibition of cyclooxygenase-2 with the selective inhibitor celecoxib demonstrated partial efficiency in reducing PJS polyposis by reducing the size but not the number of tumors (16).…”

Lipopolysaccharides Promote S-Nitrosylation and Proteasomal Degradation of Liver Kinase B1 (LKB1) in Macrophages in Vivo

“…Animals-Myeloid-specific LKB1 knock-out (KO) mice were generated as we described previously (13). All mice were housed in a controlled environment (20 Ϯ 2°C, 12-h/12-h light/dark cycle) and maintained on a standard chow diet with free access to water.…”

“…We reported previously that LKB1 suppresses LPS-induced NF-B activation and pro-inflammatory responses (13). LKB1 deficiency in macrophages results in increased production of pro-inflammatory cytokines, enzymes, and other mediators (13).…”

“…It has been implicated in a wide range of processes such as cardiac function, angiogenesis, and glucose homeostasis (10 -12). In a previous study, we found that LKB1 inhibited LPS-induced NF-B activation in macrophages (13), which revealed a novel function of LKB1 in innate immune responses. However, how LKB1 is regulated during physiological and pathological conditions remains unknown.…”

Intraventricular Injection of LKB1 Inhibits the Formation of Diet-Induced Obesity in Rats by Activating the AMPK-POMC Neurons-Sympathetic Nervous System Axis

“…LKB1 serine/threonine kinase (also known as stk11) is a tumor suppressor and a key regulator of energy metabolism [10-12]. It is expressed extensively in mammalian cells and plays important roles in various biological processes including cell polarity, cell metabolism, and cancer initiation and progression [13, 14].…”