Mycobacterium tuberculosis–Secreted Protein, ESAT-6, Inhibits Lipopolysaccharide-Induced MMP-9 Expression and Inflammation Through NF-κB and MAPK Signaling in RAW 264.7 Macrophage Cells

Ha, Sun-Hyung; Choi, Hojong; Park, Jun-Young; Abekura, Fukushi; Lee, Young Choon; Kim, Jeong-Ran; Kim, Cheorl-Ho

doi:10.1007/s10753-019-01087-x

Cited by 10 publications

(15 citation statements)

References 37 publications

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“…The mitogen-activated protein kinase (MAPK) signaling pathway is a classic inflammation-associated signaling pathway, which consists of ERK-1/2, p38 and JNK. MAPK signaling transmits stimuli signals and regulates various cellular processes, including the inflammatory response [ 18 , 19 ]. A previous study has demonstrated that inhibition of the MAPK/JNK signaling pathway and activation of the NRF2 signaling pathway attenuate lipopolysaccharide (LPS)-induced inflammation in mouse macrophages [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: The myocardial infarction-associated transcript 2 inhibits lipid accumulation and promotes cholesterol efflux in oxidized low-density lipoprotein-induced THP-1-derived macrophages via inhibiting mitogen-activated protein kinase signaling and activating the nuclear factor erythroid-related factor 2 signaling pathway

Wang

et al. 2021

Bioengineered

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Dysregulated lipid metabolism of macrophages contributes to thrombosis and antiphospholipid syndrome (APS). The long non-coding RNAs (lncRNA) myocardial infarction-associated transcript 2 (Mirt2) has been reported to inhibit inflammation and lipid accumulation; therefore, this study intended to clarify whether Mirt2 served a role in lipid metabolism. THP-1-derived macrophages with or without Mirt2-knockdown or overexpression, were exposed to oxidized low-density lipoprotein (ox-LDL), then cell migration, lipid accumulation, cholesterol efflux and inflammation were assessed using wound healing, oil red staining, commercial kits and western blot assays. Besides, ML385 was used to treat THP-1-derived macrophages to inhibit nuclear factor erythroid-related factor 2 (NRF2) expression. The expression of proteins involved in the above processes were measured by western blot. Results demonstrated that phorbol 12-myristate 13-acetate (PMA) significantly increased Mirt2 expression in THP-1 cells. Mirt2-knockdown enhanced ox-LDL-induced macrophage migration, lipid accumulation, inflammation, and inhibited cholesterol efflux. By contrast, Mirt2 overexpression displayed the opposite effects. Furthermore, Mirt2-knockdown inhibited NRF2 signaling and enhanced mitogen-activated protein kinase (MAPK) signaling, while Mirt2 overexpression displayed the opposite effects. Finally, the NRF2 inhibitor ML385 significantly reversed the above effects of Mirt2. In summary, Mirt2 served an important role in regulating lipid metabolism in macrophages via inhibiting MAPK signaling and activating the NRF2 signaling pathway.

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Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: The myocardial infarction-associated transcript 2 inhibits lipid accumulation and promotes cholesterol efflux in oxidized low-density lipoprotein-induced THP-1-derived macrophages via inhibiting mitogen-activated protein kinase signaling and activating the nuclear factor erythroid-related factor 2 signaling pathway

Wang

et al. 2021

Bioengineered

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“…Genetic deletion of LprG partially blocks phagolysosomal fusion and limits TLR2 activation 12 . In addition, another Mtb‐secreted protein, ESAT‐6, has been reported to possess anti‐inflammatory activity in a macrophage model, as previously reported by our group 2 …”

Section: Introductionsupporting

confidence: 54%

“…Mtb‐infected macrophages show attenuated phagocytic activity 21 . On the other hand, Mtb‐infected macrophages can promote antimicrobial immune responses through secretion of NO and pro‐inflammatory cytokines 2,17,21 . Furthermore, the transfer of Mtb from Mtb‐infected macrophages to surrounding uninfected macrophages has been demonstrated.…”

Section: Discussionmentioning

confidence: 99%

Mycobacterium tuberculosis glycolipoprotein LprG inhibits inflammation through NF‐κB signaling of ERK1/2 and JNK in LPS‐induced murine macrophage cells

Abekura

Park

Lim

et al. 2022

J of Cellular Biochemistry

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Mycobacterium tuberoculosis (Mtb) is a contagious pathogen that causes human tuberculosis (TB). TB is a major global health threat that causes 9.6 million illnesses and 1.5 million deaths per year. Recent studies have suggested Mtb‐secreted proteins as new candidates for therapeutic drugs and vaccines. LprG is a Mtb‐secreted surface glycolipoprotein encoded by lprG (Rv1411c), which forms an operon with Rv1410c, where Rv1410c encodes P55, an efflux pump membrane protein. Various in vitro and in vivo studies have reported on the target‐binding activity, cell envelope biosynthesis, and mycobacterial virulence of LprG. However, the anti‐inflammatory effect of LprG in macrophages has not yet been investigated. In this study, we demonstrated that LprG can suppress lipopolysaccharide (LPS)‐induced inflammation in a macrophage model. LprG inhibited LPS‐stimulated nitric oxide (NO) production. LprG also suppressed expression of inducible cyclooxygenase‐2 (COX‐2) and nitric oxide synthase (iNOS) at the transcriptional and protein levels. In addition, LprG decreased mRNA expression of the pro‐inflammatory cytokines interleukin‐1β (IL‐1β), IL‐6, and tumor necrosis factor‐α (TNF‐α). Furthermore, LprG attenuated nuclear factor kappa‐B (NF‐κB) translocation and IκB phosphorylation. Moreover, LprG specifically inhibited phosphorylated kinases such as c‐Jun N‐terminal kinase (p‐JNK) and extracellular signal‐regulated kinase 1/2 (p‐ERK1/2), but not p‐p38. Taken together, these results suggest that LprG inhibits LPS‐stimulated inflammation via downregulation of NO, COX‐2, iNOS, and pro‐inflammatory cytokines through the NF‐κB, AP‐1, and MAPK signaling pathways. The present study will aid in the development of anti‐inflammatory medications using Mtb. The organism, which has long been regarded as a human pathogenic or human health‐threating agent, can be utilized as a future medical resource.

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“…The matrix metalloproteinases (MMPs) play essential roles in cellular migration during inflammation. MMP-2 and MMP-9 are essential parts of them [ 18 ], regulating the expression of specific proteins, cyclooxygenase-2, and nitric oxide synthase, degrading various collagens and partial extracellular matrix proteins, to regulate and control the inflammatory process [ 19 ], especially in some osteoarticular diseases [ 20 ]. MMP-2 and MMP-9 were expressed in the two patients.…”

Section: Discussionmentioning

confidence: 99%

The Angiopoietin-like protein 4: a promising biomarker to distinguish brucella spondylitis from tuberculous spondylitis

Lan

Tiheiran

et al. 2021

Clin Rheumatol

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Objective The Angiopoietin-like protein 4 (ANGPTL-4) has been proved to be a protein associated with multiple inflammatory responses. Nevertheless, whether it contributes to distinguishing brucella spondylitis (BS) from tuberculous spondylitis (TS) remains an open question. Our study aim is to explore the capability of the ANGPTL-4 to differentiating BS from TS. Materials and method In our study, 53 patients were screened out according to the criteria precisely in Xinjiang Medical University Affiliated of the First Hospital from 1 January, 2016, to 31 December, 2018. Their clinical data were retrospectively reviewed. All of them underwent pathological biopsy and magnetic resonance imaging examination. All the frozen tissue sections were stained for testing ANGPTL-4. Result Among the 53 patients, BS had 26 patients, and TS had 27 patients. There was no significant difference between the baseline (P = 0.682) between the two groups. The positive rate of ANGPTL-4 in TS patients (24/27, 88.89%) was higher than that in BS patients (17/26, 65.83%) (P < 0.05). The incidence of microangiopathy and fibrous connective tissue hyperplasia in patients with BS was distinctly higher than those in the TS (P = 0.001, P = 0.008, respectively). Patients of TS frequently presented more granuloma, caseous necrosis, epithelial-like reaction, interleukin 6 (IL-6), and C-reactive protein (CRP) than those of BS. Conclusion Our study provided novel insights into distinguishing BS from TS using the ANGPTL-4 combining with histopathology, which may become new supporting evidence. Key Points• Brucella spondylitis and tuberculous spondylitis are a significant public health concern and even have prolonged damage, contributing to severe health and economic outcomes in Xinjiang of China.• The granuloma, caseous necrosis, epithelioid reaction, microangiosis, and fibrous connective tissue of pathological tissue might play a critical significance for distinguishing brucella spondylitis from tuberculous spondylitis patients.• ANGPLT-4 may become new supporting evidence identify brucella spondylitis and tuberculous spondylitis which is implicated in inflammation angiogenesis-related disorders.

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Mycobacterium tuberculosis–Secreted Protein, ESAT-6, Inhibits Lipopolysaccharide-Induced MMP-9 Expression and Inflammation Through NF-κB and MAPK Signaling in RAW 264.7 Macrophage Cells

Cited by 10 publications

References 37 publications

Mycobacterium tuberculosis glycolipoprotein LprG inhibits inflammation through NF‐κB signaling of ERK1/2 and JNK in LPS‐induced murine macrophage cells

The Angiopoietin-like protein 4: a promising biomarker to distinguish brucella spondylitis from tuberculous spondylitis

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