Use of antibiotics in the treatment of inflammatory bowel disease

Perencevich, Molly; Burakoff, Robert

doi:10.1097/01.mib.0000225330.38119.c7

Cited by 92 publications

(59 citation statements)

References 137 publications

(264 reference statements)

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“…These beneficial effects were associated with reduced iNOS and MMP expression in the intestinal tissue. Supporting these observations, Garrido-Mesa et al (2011a) confirmed the intestinal antiinflammatory effect of minocycline in experimental models of colitis in both mice and rats, showing it to have a higher efficacy than other antibiotics like metronidazole, traditionally used to treat human inflammatory bowel disease, although it was devoid of immunomodulatory properties (Perencevich and Burakoff, 2006). That study proposed that minocycline's ability to modulate both the immune and the microbiological parameters of the disease contribute to its beneficial effects.…”

Section: Effects Of Minocycline On Inflammatory Bowel Diseasesupporting

confidence: 70%

Minocycline: far beyond an antibiotic

Garrido-Mesa

Zarzuelo

Gálvez

2013

British J Pharmacology

778

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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Section: Effects Of Minocycline On Inflammatory Bowel Diseasesupporting

confidence: 70%

Minocycline: far beyond an antibiotic

Garrido-Mesa

Zarzuelo

Gálvez

2013

British J Pharmacology

778

597

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“…teria (5,34) and TLR4 antagonist Abs (35), or depletion of TLR4 (36,37) ameliorates colonic inflammation. However, depletion of commensal bacteria or TLR adaptor protein MyD88 also results in profound defects in the ability to repair DSS-induced mucosal damage (32,38).…”

Section: Discussionmentioning

confidence: 99%

Formylpeptide receptor-2 contributes to colonic epithelial homeostasis, inflammation, and tumorigenesis

Chen¹,

Liu²,

Liu³

et al. 2013

J. Clin. Invest.

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Commensal bacteria and their products provide beneficial effects to the mammalian gut by stimulating epithelial cell turnover and enhancing wound healing, without activating overt inflammation. We hypothesized that N-formylpeptide receptors, which bind bacterial N-formylpeptides and are expressed by intestinal epithelial cells, may contribute to these processes. Here we report that formylpeptide receptor-2 (FPR2), which we show is expressed on the apical and lateral membranes of colonic crypt epithelial cells, mediates N-formylpeptide-dependent epithelial cell proliferation and renewal. Colonic epithelial cells in FPR2-deficient mice displayed defects in commensal bacterium-dependent homeostasis as shown by the absence of responses to N-formylpeptide stimulation, shortened colonic crypts, reduced acute inflammatory responses to dextran sulfate sodium (DSS) challenge, delayed mucosal restoration after injury, and increased azoxymethane-induced tumorigenesis. These results indicate that FPR2 is critical in mediating homeostasis, inflammation, and epithelial repair processes in the colon.

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“…On the other hand, an increasing amount of evidence suggests that intestinal microflora may play a role in IBD pathogenesis. Therefore, antibiotics are generally used in patients with active IBD [21]. In experimental studies, IBD does not develop in murine models of colitis that are raised in a GF environment but occurs when commensal bacteria are introduced into the intestines [6,23,27].…”

Section: Discussionmentioning

confidence: 99%

Upregulation of Superoxide Dismutase Activity in the Intestinal Tract Mucosa of Germ-Free Mice

Dobashi

Yoshimura

Atarashi

et al. 2013

The Journal of Veterinary Medical Science

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ABSTRACT. Superoxide dismutase (SOD) catalyzes the breakdown of superoxide into hydrogen peroxide and oxygen in the antioxidant defense system. We had reported that the SOD activities in the ceca of germ-free (GF) mice were significantly higher than those in conventional (CV) mice. In this study, we confirmed the location where SOD activity and protein expression increased in the ceca of GF mice. An immunohistochemical analysis and total SOD activity assay were conducted using the mucosa and other remaining tissues in the ceca. In addition to SOD activity in the ceca, 4 sites of intestinal (duodenal, jejunal, ileal and colonic) mucosae in GF mice were compared with those of CV mice. Total SOD activity in the cecal mucosa of GF mice was significantly higher than that in CV mice (P<0.01), and the intensity of CuZnSOD-positive cells in cecal mucosa was increased in all GF mice. Total and CuZnSOD activities in the duodenal, jejunal, ileal, cecal and colonic mucosae of GF mice were significantly higher than those in CV mice (P<0.05, or P<0.01). Furthermore, CuZnSOD mRNA showed similar tendencies with respect to these activities. Our results suggest for the first time that upregulation of SOD activity occurs in the entire intestinal mucosa of GF mice. Antioxidant enzymes play an important role in preventing oxidative stress by acting on reactive oxidative species (ROS) generated in vivo. While physiological concentrations of ROS in vivo are beneficial and involve cell signaling pathways and survival from invading pathogens, an unbalanced, elevated levels of ROS may contribute to the development of various diseases, such as cancer, hypertension, diabetes, atherosclerosis, inflammation, and premature aging [30]. Superoxide dismutases (SODs) [16] are the most important antioxidant enzymes in the antioxidant defense system against a ROS of superoxide (O 2•− ). At present, 3 distinct SOD isoforms have been identified in mammals. One SOD isoform has Cu and Zn in its catalytic center (CuZnSOD) and exists in the intracellular cytoplasmic compartment; the second SOD isoform has manganese (Mn) in its catalytic center (MnSOD) and exists in the mitochondria of aerobic cells; and the third isoform is an extracellular SOD [30]. SODs are the first line of defense for dismutation of excess O 2•− , which causes tissue disorders, as SODs convert O 2•− to molecular oxygen and H 2 O 2 [22]. Of the different SOD enzymes, CuZnSOD is the most abundant and widely distributed enzyme in many tissues [13].We recently reported that total SOD, CuZnSOD and MnSOD activities in the ceca of germ-free (GF) mice were significantly higher than those in the ceca of conventional (CV) mice [7]. CuZnSOD mRNA expression in the ceca of GF mice was significantly higher than that in CV mice, and CuZnSOD protein expression showed similar tendencies. Consistent with these results, the total SOD activity in conventionalized (CVz) mice decreased to the level of total SOD activity observed in the ceca of CV mice. These results suggested that the antioxidant defense ...

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Use of antibiotics in the treatment of inflammatory bowel disease

Cited by 92 publications

References 137 publications

Minocycline: far beyond an antibiotic

Minocycline: far beyond an antibiotic

Formylpeptide receptor-2 contributes to colonic epithelial homeostasis, inflammation, and tumorigenesis

Upregulation of Superoxide Dismutase Activity in the Intestinal Tract Mucosa of Germ-Free Mice

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