Minocycline attenuates experimental colitis in mice by blocking expression of inducible nitric oxide synthase and matrix metalloproteinases

Huang, Tseng; Chu, Heng-Cheng; Lin, Yi-Ling; Lin, Chih-Kung; Hsieh, Tsai‐Yuan; Chang, Wei‐Kuo; Chao, You‐Chen; Liao, Ching‐Len

doi:10.1016/j.taap.2009.02.026

Cited by 55 publications

(46 citation statements)

References 71 publications

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“…In our study, MMP-2, but not MMP-9 deficiency resulted in less influx of macrophages into the colon as indicated by significantly lower F4/80 + cell numbers in the colonic lamina propria and submucosa at day 8 which was paralleled by reduced cytokine expression in colon biopsies. Furthermore, we [18] and others [30,31] could show in acute experimental colitis that following MMP blockage and, as depicted in the presented study, in MMP-2-, but not MMP-9-deficient mice, the influx of neutrophilic granulocytes into the colon is diminished: An effect that, in turn, results in reduced oxidative stress for the colonic epithelium. In addition, these effects were paralleled by less infiltration of the colonic lamina propria and submucosa by T-lymphocytes including Tregs as well as B-cells.…”

Section: Discussionsupporting

confidence: 78%

The distinct roles of MMP-2 and MMP-9 in acute DSS colitis

Heimesaat¹,

Dunay²,

Fuchs³

et al. 2011

European Journal of Microbiology and Immunology

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Expression of gelatinases A and B, also referred to matrixmetalloproteinases (MMP)-2 and -9, respectively, is increased in inflamed tissues of experimental intestinal inflammation and humans with inflammatory bowel disease (IBDs). Given that we recently reported that treatment with the selective gelatinase inhibitor RO28-2653 ameliorates acute dextrane sulfate sodium (DSS) colitis, we asked whether gelatinase A or B expression is pivotal in mediating large intestinal inflammation. Results from our study reveal that symptoms of acute DSS colitis as well as histopathological colonic changes were ameliorated in MMP-2-, but not MMP-9-deficient mice, and were paralleled by a diminished influx of immune cells. In MMP-2-deficient mice, we observed lower expression of pro-inflammatory cytokines including interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and IL-6 in colonic biopsies and less overgrowth of the colonic lumen by potentially pro-inflammatory enterobacteria from the commensal gut microbiota. We conclude that rather MMP-2 than MMP-9 is causative for the establishment of DSS colitis in mice. The discrepancy of these data to prior reports might be due to substantial differences in the intestinal microbiota composition of the mice bred at different animal facilities impacting susceptibility to inflammatory stimuli. Consequently, a detailed survey of the gut microbiota should be implemented in immunological/inflammatory studies in the future in order to allow comparison of data from different facilities.

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Section: Discussionsupporting

confidence: 78%

The distinct roles of MMP-2 and MMP-9 in acute DSS colitis

Heimesaat¹,

Dunay²,

Fuchs³

et al. 2011

European Journal of Microbiology and Immunology

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“…The effects of minocycline on experimental colitis were first described in 2009 by Huang et al (2009b), who reported its ability to prevent and treat dextran sodium sulphate-induced colitis, significantly diminishing the mortality rate and attenuating the severity of the disease. These beneficial effects were associated with reduced iNOS and MMP expression in the intestinal tissue.…”

Section: Effects Of Minocycline On Inflammatory Bowel Diseasementioning

confidence: 99%

“…These preclinical studies have prompted the evaluation of minocycline in clinical trials in patients with neuronal disease, where it has shown promising neuroprotective properties (Lampl et al, 2007). Moreover, the growing interest in minocycline has led to evaluations of its therapeutic efficacy in many other experimental disease models, such as inflammatory bowel disease (Huang et al, 2009b;Garrido-Mesa et al, 2011a,b), diabetes (Bain et al, 1997;Wang et al, 2003;Cai et al, 2011), fragile X syndrome (FXS) (Paribello et al, 2010), cardiac ischaemia (Scarabelli et al, 2004) and human immunodeficiency virus (HIV) infection (Szeto et al, 2010;Campbell et al, 2011) (Figure 2).…”

Section: Introductionmentioning

confidence: 99%

Minocycline: far beyond an antibiotic

Garrido-Mesa

Zarzuelo

Gálvez

2013

British J Pharmacology

740

597

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Minocycline is a second‐generation, semi‐synthetic tetracycline that has been in therapeutic use for over 30 years because of its antibiotic properties against both gram‐positive and gram‐negative bacteria. It is mainly used in the treatment of acne vulgaris and some sexually transmitted diseases. Recently, it has been reported that tetracyclines can exert a variety of biological actions that are independent of their anti‐microbial activity, including anti‐inflammatory and anti‐apoptotic activities, and inhibition of proteolysis, angiogenesis and tumour metastasis. These findings specifically concern to minocycline as it has recently been found to have multiple non‐antibiotic biological effects that are beneficial in experimental models of various diseases with an inflammatory basis, including dermatitis, periodontitis, atherosclerosis and autoimmune disorders such as rheumatoid arthritis and inflammatory bowel disease. Of note, minocycline has also emerged as the most effective tetracycline derivative at providing neuroprotection. This effect has been confirmed in experimental models of ischaemia, traumatic brain injury and neuropathic pain, and of several neurodegenerative conditions including Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, Alzheimer's disease, multiple sclerosis and spinal cord injury. Moreover, other pre‐clinical studies have shown its ability to inhibit malignant cell growth and activation and replication of human immunodeficiency virus, and to prevent bone resorption. Considering the above‐mentioned findings, this review will cover the most important topics in the pharmacology of minocycline to date, supporting its evaluation as a new therapeutic approach for many of the diseases described herein.

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“…Additional groups of mice received 10 mg/kg minocycline (SigmaAldrich) or saline intraperitoneally 1 h prior to the OVA challenge. This dose of minocycline was selected on the basis of studies that demonstrated its protective effect in a variety of models of inflammation (17)(18)(19). Mice were then left to recover and were sacrificed 24 h or 48 h later for bronchio-alveolar lavage (BAL) or lung fixation and processing for histological analysis.…”

Section: Animals Protocols For Sensitization and Challenge Andmentioning

confidence: 99%

Minocycline Blocks Asthma-associated Inflammation in Part by Interfering with the T Cell Receptor-Nuclear Factor κB-GATA-3-IL-4 Axis without a Prominent Effect on Poly(ADP-ribose) Polymerase

Naura

Kim

et al. 2013

Journal of Biological Chemistry

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Background: Minocycline protects against asthma independently of its antibiotic function. Results: Minocycline blocks asthma-associated traits, including IgE production, by modulating the TCR-NF-B-GATA-3-IL-4 axis but not the TCR/NFAT1/IL-2 pathway without a direct effect on PARP activity. Conclusion: These results provide new insight into the mechanism of action of minocycline. Significance: These results provide further support to the therapeutic potential of minocycline in reducing or preventing allergen-induced asthma symptoms.

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Minocycline attenuates experimental colitis in mice by blocking expression of inducible nitric oxide synthase and matrix metalloproteinases

Cited by 55 publications

References 71 publications

The distinct roles of MMP-2 and MMP-9 in acute DSS colitis

The distinct roles of MMP-2 and MMP-9 in acute DSS colitis

Minocycline: far beyond an antibiotic

Minocycline Blocks Asthma-associated Inflammation in Part by Interfering with the T Cell Receptor-Nuclear Factor κB-GATA-3-IL-4 Axis without a Prominent Effect on Poly(ADP-ribose) Polymerase

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