Effect of adrenomedullin administration on acetic acid-induced colitis in rats

Ashizuka, Shinya; Ishikawa, Naoto; Kato, Jun; Yamaga, Junichi; Inatsu, Haruhiko; Eto, Tanenao; Kïtamura, Kazuo

doi:10.1016/j.peptides.2005.05.007

Cited by 40 publications

(40 citation statements)

References 34 publications

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“…It down-regulates TNF-a expression in macrophages 16 and exerts a protective effect in experimental colitis. 17 It also exerts beneficial effects in rheumatoid arthritis models. 18,19 Gonzalez-Rey et al 20 demonstrated that intraperitoneal AM administration correlated with a reduction in disease severity, together with a T helper type 1 (Th1) to Th2 switch and Treg cell induction.…”

Section: Introductionmentioning

confidence: 99%

Adrenomedullin, a neuropeptide with immunoregulatory properties induces semi‐mature tolerogenic dendritic cells

et al. 2012

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SummaryDendritic cells (DC) play a pivotal role in tolerance. Adrenomedullin (AM), a neuropeptide with anti-apoptotic and anti-inflammatory effects, may decrease T helper type 1 effector cells and induce regulatory T (Treg) cells. The aim of this study was to evaluate AM effects on murine dendritic cell (DC) maturation and functions. Bone marrow-derived DC were produced and stimulated with CpG motifs, lipopolysaccharide or AM for 24 hr. Then, DC maturation and expression of AM and AM receptors were evaluated. Compared with lipopolysaccharide-stimulated or CpGstimulated DC, AM-stimulated DC had lower levels of co-stimulatory molecule expression and pro-inflammatory cytokine release. The AM induced high levels of interferon-c but not of interleukin-10. Importantly, AM inhibited lipopolysaccharide-induced maturation of DC. However, allogeneic T-cell stimulation and endocytic capacity of AM-stimulated DC were comparable to those of semi-mature and mature DC. Moreover, DC expressed AM and its receptors at a basal level, and AM receptor expression increased with DC maturation. The AM stimulation induced indoleamine 2,3-dioxygenase (IDO) expression, promoting Treg cell expansion. For the first time, we describe the DC maturation phenotype by a neuropeptide (AM). We have demonstrated that AM and its receptors are expressed in DC and that exogenous AM can modify the DC phenotype and functions and can induce a semi-mature DC phenotype with IDO expression. These results indicate close interactions among immune system regulation mechanisms and calcitonin-like peptides.

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Section: Introductionmentioning

confidence: 99%

Adrenomedullin, a neuropeptide with immunoregulatory properties induces semi‐mature tolerogenic dendritic cells

et al. 2012

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“…Since its isolation, AM has been shown to be widely distributed among various organs and tissues, including the human digestive system, and to be involved in a variety of physiological functions such as vasodilatation, hormone secretion, neurotransmission, embryogenesis, wound healing, and immunoregulation 5 . In our previous study, we report that AM reduces the severity of acetic acid-induced colitis in rats 6 . Experimental animal models are important tools that provide various results us to research the pathogenesis of diseases and to test emerging therapeutic strategies.…”

Section: Introductionmentioning

confidence: 85%

“…Sections (5 µm) were stained with hematoxylin and eosin, then processed for histological examin standard techniques 6 .…”

Section: Histological Analysismentioning

confidence: 99%

Effect of Adrenomedullin Administration in Two Rat Models of Experimental Inflammatory Bowel Disease

Nagata¹

2015

AJLS

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Adrenomedullin (AM) is a novel hypotensive peptide that also exerts powerful anti-inflammatory effects. We recently showed that AM significantly reduces the clinical severity of acetic acid-induced colitis, an experimental model of inflammatory bowel disease (IBD) in rats. In the present study, we examined the effect of AM in two alternative rat models of IBD. We found that 2,4,6-trinitrobenzenesulfonic acid (TNBS) induced megacolon development in the saline-treated group, but AM treatment reduced the macroscopic damage caused by TNBS. In the dextran sulfate sodium (DSS) model, treatment with AM reduced diarrhea and bloody stool scores, but did not reduce body weight. Histological analysis revealed that in both the TNBS and DSS models, colon inflammation was much more severe in the saline-treated group than in the AM-treated group. These findings indicate that the anti-inflammatory properties of AM make it an effective therapeutic agent for the treatment of IBD in rats.

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“…Although little is understood about the physiological and pathophysiological functions of AM in the gastrointestinal tract, these fi ndings suggest that endogenously expressed AM in the colon could play an important protective role against infl ammatory bowel diseases. To test this hypothesis, we assessed the effect of synthetic AM on acetic acid-induced colitis and cytokine production [ 31 ]. Colitis was induced using the method of Kojima et al [ 32 ], after which AM or saline was administered anally once a day for 3-10 days.…”

Section: Preclinical Pharmacological Effect Of Am In Experimental Modmentioning

confidence: 99%

Adrenomedullin as a Potential Therapeutic Agent for Refractory Ulcerative Colitis

Kïtamura

Ashizuka

Inatsu

et al. 2015

Innovative Medicine

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Adrenomedullin (AM) was originally isolated from human pheochromocytoma as a biologically active peptide with potent vasodilating action, but it also has a wide range of physiological properties including cardiovascular protection, neovascularization, and the ability to suppress apoptosis. It is constitutively produced by various tissues including the gastrointestinal tract. AM production and secretion can be induced by pro-infl ammatory cytokines such as tumor necrosis factor-α and interleukin-1, as well as by lipopolysaccharide. Conversely, AM causes the downregulation of infl ammatory cytokines in cultured cells and downregulates inflammatory processes in various models of colitis, including those induced by acetic acid and by dextran sulfate sodium. AM works by exerting anti-infl ammatory and antibacterial effects and by stimulating mucosal regeneration and supporting maintenance of the colonic epithelial barrier. The present fi ndings suggest that AM could serve as a novel agent for treating refractory ulcerative colitis.

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Effect of adrenomedullin administration on acetic acid-induced colitis in rats

Cited by 40 publications

References 34 publications

Adrenomedullin, a neuropeptide with immunoregulatory properties induces semi‐mature tolerogenic dendritic cells

Adrenomedullin, a neuropeptide with immunoregulatory properties induces semi‐mature tolerogenic dendritic cells

Effect of Adrenomedullin Administration in Two Rat Models of Experimental Inflammatory Bowel Disease

Adrenomedullin as a Potential Therapeutic Agent for Refractory Ulcerative Colitis

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