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Liver kinase B1 overexpression controls mycobacterial infection in macrophages via FOXO1/Wnt5a signaling
Author(s) -
Cui Junwei,
Li Mingying,
Liu Weiguo,
Zhang Bianfang,
Sun Bing,
Niu Wenyi,
Wang Yongliang
Publication year - 2019
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.27322
Subject(s) - inflammation , macrophage , tumor necrosis factor alpha , nitric oxide , nitric oxide synthase , biology , cytokine , mycobacterium tuberculosis , foxo1 , kinase , immunology , foam cell , cancer research , signal transduction , tuberculosis , microbiology and biotechnology , medicine , endocrinology , protein kinase b , biochemistry , pathology , in vitro
Mycobacterium tuberculosis (Mtb) is a primary cause of tuberculosis (TB), which has infected more than one‐third of the world’s population. Mtb survival and subsequent inflammation in macrophages are important components of TB. Liver kinase B1 (LKB1) has demonstrated anti‐inflammation effects, but its function and underlying mechanism in mycobacteria‐infected macrophages remains unknown. In the current study, we discovered that LKB1 was markedly decreased in Mtb‐infected THP‐1 and U937 macrophages. Moreover, LKB1 overexpression inhibited Mtb survival in macrophages. Mtb infection increased expression of nitric oxide, inducible nitric oxide synthase, and inflammation‐related cytokines interleukin (IL)‐6, tumor necrosis factor‐α, and IL‐1β, whereas pcDNA3‐LKB1 transfection inhibited the release of these cytokines in THP‐1 and U937 cells. Furthermore, LKB1 overexpression significantly decreased protein expression of Wnt5a, which is dependent on the elevation of forkhead box protein O1 (FOXO1). Generally, we show that interruption of FOXO1 or overexpression of Wnt5a can reverse the effects of LKB1 on mycobacterial intracellular survival, nitric oxide, inducible nitric oxide synthase expression, and inflammatory cytokine release. These findings indicate important roles for LKB1, FOXO1, and Wnt5a in controlling mycobacteria and cell inflammation.