Relative contributions of NOS isoforms during experimental colitis: endothelial-derived NOS maintains mucosal integrity

Vallance, Bruce A.; Dijkstra, Gerard; Qiu, Bosheng; Waaij, Laurens A. van der; Goor, Harry van; Jansen, Petér L. M.; Mashimo, Hiroshi; Collins, Stephen M.

doi:10.1152/ajpgi.00187.2004

Cited by 70 publications

(52 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…NO plays a crucial role in the gastrointestinal tract. 27) eNOS is an enzyme which mostly localizes to vascular endothelial cells and produces NO all the time. In a recent study, it was found that this enzyme is also expressed in gastrointestinal mucosal cells.…”

Section: Discussionmentioning

confidence: 99%

Effect of Nitric Oxide on .BETA.-Glucan/Indomethacin-Induced Septic Shock

Nameda

Saito

Miura

et al. 2005

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

Nitric oxide (NO) is an important defense molecule in the nonspecific immune system of the body.1,2) However, NO also acts as a mediator of tissue damage in inflammatory diseases.3) NO is a highly reactive molecule that is normally produced from L-arginine by NO synthase (NOS). There are three isoforms of NOS: neuronal NOS (nNOS), endothelial NOS (eNOS), and inducible NOS (iNOS). nNOS and eNOS are constitutively expressed, whereas iNOS expression is induced by stimuli such as lipopolysaccharide (LPS) and cytokines. 4,5) Large amounts of NO produced by iNOS have been shown to play a major role in sepsis and endotoxin shock. 6)Septic shock is characterized by a systemic inflammatory response syndrome. Sepsis associated with multiple organ failure and dysfunction, leads to hypotension. 7) NO is a strong mediator of vasodilation. 8)During the last decade, NO has been demonstrated to have a role in septic shock in both humans and experimental animals.9-11) NOS inhibitors have been used to treat septic shock. Indeed, it was reported that a NOS inhibitor restored hypotension in sepsis, but also had a detrimental effect. [12][13][14] Thus, the role of NO in septic shock has not been clarified. The apparent complexity of NO inhibition may be due in part to the different models of sepsis used. Generally, LPS is used to induce septic shock, however, it can not reproduce both gram-positive and -negative sepsis. We developed an animal model of sepsis in mice using two drugs, indomethacin (IND) and b-glucan, sonifilan (SPG). This model uses endogenous LPS which is contained in enteric bacterial flora.We have previously examined the activities of various bglucans [15][16][17][18][19] and found that pretreatment with b-glucan significantly increased mortality on the subsequent administration of IND in mice. [20][21][22][23] The lethality would be closely related to the translocation of enterobacterial flora to the peritoneal cavity. Since the concentrations of IFN-g, IL-6, and CSF in sera of b-glucan/IND-treated mice were significantly elevated, the mortality was likely due to a mal-adjustment of the cytokine network. A precise characterization of this model is needed to clarify the mechanism of septic shock. In this study, we examined the effect of NO on this model by inhibiting the synthesis of NO with a NOS inhibitor. MATERIALS AND METHODS AnimalsMale ICR mice between 5 and 8 weeks of age were purchased from Japan SLC, Inc., Shizuoka and maintained under specific pathogen-free conditions. The breeding and handling of all animals in this experiment were approved by the Committee on Animal Experiments of the School of Pharmacy, Tokyo University of Pharmacy and Life Science.Reagents Sonifilan (SPG) was purchased from Kaken Pharmaceutical Co. (Tokyo, Japan). N G -nitro-L-arginine methyl ester (L-NAME), aminoguanidine (AG) and indomethacin (IND) were obtained from Wako Pure Chemical Ind. IND was suspended with 2% polyoxyethylene (20) sorbitan monooleate in 0.5% sodium carboxymetyl cellulose (CMC).Administration of SPG/Indomethaci...

show abstract

Section: Discussionmentioning

confidence: 99%

Effect of Nitric Oxide on .BETA.-Glucan/Indomethacin-Induced Septic Shock

Nameda

Saito

Miura

et al. 2005

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

show abstract

“…eNOS is a constitutive source of NO whereas iNOS is an inducible generator of NO during disease pathology (103,108,109). Genetic deletion of eNOS expression in the endothelium in the DSS and TNBS models resulted in increased disease activity, suggesting a protective role for eNOS derived NO acting in antioxidant, anti-inflammatory roles (132,133,161). Krieglstein et al (80,81) have also shown that loss of iNOS is protective in DSS colitis; they suggest that iNOSderived NO may be pathogenic and that tissue-derived iNOS makes a larger contribution to inflammatory cell recruitment than blood cell-derived iNOS.…”

Section: Angiogenic Mediators In Ibd and Experimental Colitismentioning

confidence: 99%

Pathogenic angiogenesis in IBD and experimental colitis: new ideas and therapeutic avenues

Chidlow

Shukla²,

Grisham³

et al. 2007

American Journal of Physiology-Gastrointestinal and Liver Physi

144

114

View full text Add to dashboard Cite

Chidlow JH Jr, Shukla D, Grisham MB, Kevil CG. Pathogenic angiogenesis in IBD and experimental colitis: new ideas and therapeutic avenues. Am J Physiol Gastrointest Liver Physiol 293: G5-G18, 2007. First published April 26, 2007; doi:10.1152/ajpgi.00107.2007.-Angiogenesis is now understood to play a major role in the pathology of chronic inflammatory diseases and is indicated to exacerbate disease pathology. Recent evidence shows that angiogenesis is crucial during inflammatory bowel disease (IBD) and in experimental models of colitis. Examination of the relationship between angiogenesis and inflammation in experimental colitis shows that initiating factors for these responses simultaneously increase as disease progresses and correlate in magnitude. Recent studies show that inhibition of the inflammatory response attenuates angiogenesis to a similar degree and, importantly, that inhibition of angiogenesis does the same to inflammation. Recent data provide evidence that differential regulation of the angiogenic mediators involved in IBD-associated chronic inflammation is the root of this pathological angiogenesis. Many factors are involved in this phenomenon, including growth factors/cytokines, chemokines, adhesion molecules, integrins, matrix-associated molecules, and signaling targets. These factors are produced by various vascular, inflammatory, and immune cell types that are involved in IBD pathology. Moreover, recent studies provide evidence that antiangiogenic therapy is a novel and effective approach for IBD treatment. Here we review the role of pathological angiogenesis during IBD and experimental colitis and discuss the therapeutic avenues this recent knowledge has revealed. inflammation; T cells; growth factors; adhesion molecules; antiangiogenesis ANGIOGENESIS PLAYS AN IMPORTANT role in many chronic inflammatory diseases including but not limited to diabetic retinopathy, atherosclerosis, rheumatoid arthritis, hypercholesterolemia, and psoriasis. It has been suggested that the angiogenic components of these diseases contribute to and exacerbate disease conditions (26, 31). Recent findings, both clinical and experimental, indicate that angiogenesis also plays a crucial role in the inflammatory bowel diseases (IBD), consisting of Crohn's disease (CD) and ulcerative colitis (UC) (31,37,58,131,155). Development of new vasculature during chronic inflammation may play a negative "pathological" role by contributing to increased inflammatory responses due to dysfunctional new vessel architecture and increases in the recruitment of inflammatory cell types. Importantly, recent data have shown that angiogenic inhibition during chronic inflammatory diseases attenuates further inflammation and disease pathology (31, 37, 51). As such, expanding our knowledge of how pathological angiogenesis occurs during IBD will further our ability to treat patients with these diseases. IBD PathogenesisCD and UC are idiopathic inflammatory disorders of the intestine and/or colon in which patients suffer from rectal bleeding, severe...

show abstract

“…A béltraktusban mindhárom NOS izoforma megtalálható mind a kapillárisok endotéljében, a bélidegrendszer neuronjaiban és a bélfal izomzatában, azonban eloszlásuk, funkciójuk és aktivitásuk eltérő mértékben változik a fiziológiás és patológiás folyamatokban (Vannucchi, Corsani et al 2002, Vallance, Dijkstra et al 2004, Van Geldre, Fraeyman et al 2004, Talapka, Bodi et al 2011, Baccari, Traini et al 2012. Eddigi ismereteink alapján a konstitutív izoformáknak a bélrendszer fiziológiás állapotának fenntartásában betöltött szerepük, hogy szabályozzák az epitél réteg permeabilitását.…”

Section: Nos Izoformák a Béltraktusbanunclassified

“…dextrán szodium szulfát indukálta vastagbélgyulladásban nem mértek szignifikáns változást a nNOS mRNS-ének expressziójában, ugyanakkor a gyulladt területeken a nNOS fehérje nagyobb mennyiségben volt detektálható (Beck, Xavier et al 2004). Kísérletes vastagbélgyulladásban az eNOS fehérje mennyisége jelentősen megnő az endotél sejtekben (Beck, Xavier et al 2004, Vallance, Dijkstra et al 2004). Azért, hogy jobban megértsük, hogy az egyes izoformák milyen szerepet játszanak a gyulladás folyamatában, génmódosított egereken végeztek kísérleteket.…”

Section: Nos Izoformák a Béltraktusbanunclassified

“…kísérleteiben az eNOS és az iNOS is protektívnek bizonyult, míg a nNOS génkiütött állatokban súlyosabb bélgyulladást kaptak (Beck, Xavier et al 2004). Több kutatócsoport pedig épp az ellenkezőjéről számol be, az eNOS illetve az iNOS génmódosított egerekben egyaránt súlyosabb gyulladást tapasztaltak a vad típushoz képest (McCafferty, Miampamba et al 1999, Sasaki, Bharwani et al 2003, Vallance, Dijkstra et al 2004. Így az egyes izoformáknak a bélgyulladás pathomechanizmusában betöltött pontos szerepének tisztázása további kísérleteket igényel.…”

Section: Nos Izoformák a Béltraktusbanunclassified

See 1 more Smart Citation

A szabadidős mozgás kardiovaszkuláris és vastagbélgyulladást csökkentő hatása patkányban: a hem-oxigenáz és a nitrogénmonoxid-szintáz enzimek szerepe

Szalai

View full text Add to dashboard Cite

Relative contributions of NOS isoforms during experimental colitis: endothelial-derived NOS maintains mucosal integrity

Cited by 70 publications

References 59 publications

Effect of Nitric Oxide on .BETA.-Glucan/Indomethacin-Induced Septic Shock

Effect of Nitric Oxide on .BETA.-Glucan/Indomethacin-Induced Septic Shock

Pathogenic angiogenesis in IBD and experimental colitis: new ideas and therapeutic avenues

A szabadidős mozgás kardiovaszkuláris és vastagbélgyulladást csökkentő hatása patkányban: a hem-oxigenáz és a nitrogénmonoxid-szintáz enzimek szerepe

Contact Info

Product

Resources

About