Doxycycline Inhibits IL-17-Stimulated MMP-9 Expression by Downregulating ERK1/2 Activation: Implications in Myogenic Differentiation

Obradović, Hristina; Krstić, Jelena; Кукољ, Тамара; Trivanović, Drenka; Okić-Đorđević, Ivana; Mojsilović, Slavko; Jauković, Aleksandra; Jovčić, Gordana; Bugarski, Diana; Santibáñez, Juan F.

doi:10.1155/2016/2939658

Cited by 16 publications

(21 citation statements)

References 40 publications

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“…Recent reports have demonstrated that MAPK-dependent pathways are involved in thrombin-induced MMP-9 expression in various cell types [38,39,40]. Our recent data have also revealed that MAPKs participate in the thrombin-induced MMP-9 expression in SK-N-SH cells [20,21].…”

Section: Resultsmentioning

confidence: 53%

Galangin Inhibits Thrombin-Induced MMP-9 Expression in SK-N-SH Cells via Protein Kinase-Dependent NF-κB Phosphorylation

Yang

Lin

Hsiao

et al. 2018

IJMS

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Galangin, a member of the flavonol compounds of the flavonoids, could exert anti-inflammatory effects in various cell types. It has been used for the treatment of arthritis, airway inflammation, stroke, and cognitive impairment. Thrombin, one of the regulators of matrix metalloproteinase (MMPs), has been known as a vital factor of physiological and pathological processes, including cell migration, the blood–brain barrier breakdown, brain edema formation, neuroinflammation, and neuronal death. MMP-9 especially may contribute to neurodegenerative diseases. However, the effect of galangin in combating thrombin-induced MMP-9 expression is not well understood in neurons. Therefore, we attempted to explore the molecular mechanisms by which galangin inhibited MMP-9 expression and cell migration induced by thrombin in SK-N-SH cells (a human neuroblastoma cell line). Gelatin zymography, western blot, real-time PCR, and cell migration assay were used to elucidate the inhibitory effects of galangin on the thrmbin-mediated responses. The results showed that galangin markedly attenuated the thrombin-stimulated phosphorylation of proto-oncogene tyrosine-protein kinase (c-Src), proline-rich tyrosine kinase 2 (Pyk2), protein kinase C (PKC)α/β/δ, protein kinase B (Akt), mammalian target of rapamycin (mTOR), p42/p44 mitogen-activated protein kinase (MAPK), Jun amino-terminal kinases (JNK)1/2, p38 MAPK, forkhead box protein O1 (FoxO1), p65, and c-Jun and suppressed MMP-9 expression and cell migration in SK-N-SH cells. Our results concluded that galangin blocked the thrombin-induced MMP-9 expression in SK-N-SH cells via inhibiting c-Src, Pyk2, PKCα/βII/δ, Akt, mTOR, p42/p44 MAPK, JNK1/2, p38 MAPK, FoxO1, c-Jun, and p65 phosphorylation and ultimately attenuated cell migration. Therefore, galangin may be a potential candidate for the management of brain inflammatory diseases.

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Section: Resultsmentioning

confidence: 53%

Galangin Inhibits Thrombin-Induced MMP-9 Expression in SK-N-SH Cells via Protein Kinase-Dependent NF-κB Phosphorylation

Yang

Lin

Hsiao

et al. 2018

IJMS

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“…Furthermore, IL-17 increases in vivo tumor growth in human nonsmall cell lung cancer (NSCLC) in SCID mice through CXCR-2-dependent angiogenesis [183]. MMP-9, MMP-2 via NF-kB/hypoxia-inducible factor (HIF-1a) pathway is increased by IL-17 in rheumatoid arthritis, promoting cell migration [184], and MMP-9 through mitogen-activated protein kinase 3 (ERK1) and mitogen-activated protein kinase 1 (ERK2) MAPK activation [185].…”

Section: Disruption Of Gut Bacteria Composition As Internal Pathogenimentioning

confidence: 99%

Chronic inflammation evoked by pathogenic stimulus during carcinogenesis

Brücher

Jamall

2019

4open

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A pathogenic (biological or chemical) stimulus is the earliest information received by a cell that can result in the disruption of homeostasis with consequent development of disease. Chronic inflammation involves many cell types with numerous cytokines and signaling pathways, the release of different components by the cells, and the crosstalk provoked by such stimuli involving subclinical chronic inflammation and is mechanistically manifold. Exosomes secrete chemicals that trigger the epithelium to produce exosome-like nanoparticles promoting chronic inflammation. Small molecules, together with various cytokines, selectively target signaling pathways inducing crosstalk that suppress apoptosis. 16S rRNA gene sequencing has become routine to provide information on the composition and abundance of bacteria found in human tissues and in reservoirs. The deregulation of autophagy with chronic stimulation of inflammation is an early phenomenon in carcinogenesis. The disruption of cell–cell integrity enables transcellular CagA migration and triggers deregulation of autophagy with the net result being chronic inflammation. The complex and insidious nature of chronic inflammation can be seen both inside and outside the cell and even with intracellular nuclear fragments such as chromatin, which itself can elicit a chronic inflammatory response within the cytoplasm and affect autophagy. The ultimate result of unresolved chronic inflammation is fibrosis, a step before tissue remodeling results in the formation of a precancerous niche (PCN). Various pathogenic stimuli associated with different neoplasms result in persistent inflammation. This ongoing disruption of homeostasis in the micromilieu of cells, tissues, and organs is an essential preamble to carcinogenesis and occurs early in that process.

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“…Indeed, doxycycline treatment did not elicit a reduction in myosin heavy chain content in C2C12 cultured myotubes, but instead caused hypertrophy and increased myosin heavy chain content (Obradović et al, 2016). However, Obradović et al (2016) FIGURE 4 | Minocycline treatment (10 µg/mL) for 48 h decreases protein synthesis and myosin heavy chain abundance in cultured C2C12 myotubes. (A,B) Protein synthesis was reduced by 23% with 48 h minocycline treatment (10 µg/mL), as measured via puromycin incorporation in C2C12 myotubes.…”

Section: Discussionmentioning

confidence: 98%

“…Oral minocycline treatment improved grip strength, but not muscle mass in response to cancer cachexia in mice despite reducing neural inflammation ( Norden et al, 2015 ), and tetracycline injection did not prevent atrophy caused by external fixation, a form of limb immobilisation, despite improving expression of myogenic proteins ( Shefer et al, 2008 ). In contrast, Obradović et al (2016) reported hypertrophy with tetracycline treatment in cultured skeletal muscle, and in a mouse model of muscular dystrophy type 1A either minocycline or doxycycline treatment enhanced lifespan, and doxycycline treatment reduced the severity of muscle atrophy ( Girgenrath et al, 2009 ). However, in this study they were not able to identify whether the mechanism of protection was neural or myogenic.…”

Section: Introductionmentioning

confidence: 96%

Minocycline Treatment Reduces Mass and Force Output From Fast-Twitch Mouse Muscles and Inhibits Myosin Production in C2C12 Myotubes

et al. 2021

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Minocycline, a tetracycline-class of antibiotic, has been tested with mixed effectiveness on neuromuscular disorders such as amyotrophic lateral sclerosis, autoimmune neuritis and muscular dystrophy. The independent effect of minocycline on skeletal muscle force production and signalling remain poorly understood. Our aim here is to investigate the effects of minocycline on muscle mass, force production, myosin heavy chain abundance and protein synthesis. Mice were injected with minocycline (40 mg/kg i.p.) daily for 5 days and sacrificed at day six. Fast-twitch EDL, TA muscles and slow-twitch soleus muscles were dissected out, the TA muscle was snap-frozen and the remaining muscles were attached to force transducer whilst maintained in an organ bath. In C2C12 myotubes, minocycline was applied to the media at a final concentration of 10 μg/mL for 48 h. In minocycline treated mice absolute maximal force was lower in fast-twitch EDL while in slow-twitch soleus there was an increase in the time to peak and relaxation of the twitch. There was no effect of minocycline treatment on the other contractile parameters measured in isolated fast- and slow-twitch muscles. In C2C12 cultured cells, minocycline treatment significantly reduced both myosin heavy chain content and protein synthesis without visible changes to myotube morphology. In the TA muscle there was no significant changes in myosin heavy chain content. These results indicate that high dose minocycline treatment can cause a reduction in maximal isometric force production and mass in fast-twitch EDL and impair protein synthesis during myogenesis in C2C12 cultured cells. These findings have important implications for future studies investigating the efficacy of minocycline treatment in neuromuscular or other muscle-atrophy inducing conditions.

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Doxycycline Inhibits IL-17-Stimulated MMP-9 Expression by Downregulating ERK1/2 Activation: Implications in Myogenic Differentiation

Cited by 16 publications

References 40 publications

Galangin Inhibits Thrombin-Induced MMP-9 Expression in SK-N-SH Cells via Protein Kinase-Dependent NF-κB Phosphorylation

Galangin Inhibits Thrombin-Induced MMP-9 Expression in SK-N-SH Cells via Protein Kinase-Dependent NF-κB Phosphorylation

Chronic inflammation evoked by pathogenic stimulus during carcinogenesis

Minocycline Treatment Reduces Mass and Force Output From Fast-Twitch Mouse Muscles and Inhibits Myosin Production in C2C12 Myotubes

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