PS1-01 Nitric oxide modulation by retinoic acid, IL-17A and TNF-α in PBMC and colonic mucosa cultures from Algerian patients with inflammatory bowel disease

Increased amounts of PGE2 have been detected in the inflamed mucosa of patients with inflammatory bowel disease (IBD). This increase has been attributed to enhanced synthesis rather than reduced catabolism of PGE2. 15-Hydroxyprostaglandin dehydrogenase (15-PGDH) plays a major role in the catabolism of PGE2. In this study, we investigated whether amounts of 15-PGDH were altered in inflamed mucosa from patients with IBD. Amounts of 15-PGDH protein and mRNA were markedly reduced in inflamed mucosa from patients with Crohn's disease and ulcerative colitis. In situ hybridization demonstrated that 15-PGDH was expressed in normal colonic epithelium but was virtually absent in inflamed colonic mucosa from IBD patients. Because of the importance of TNF-α in IBD, we also determined the effects of TNF-α on the expression of 15-PGDH in vitro. Treatment with TNF-α suppressed the transcription of 15-PGDH in human colonocytes, resulting in reduced amounts of 15-PGDH mRNA and protein and enzyme activity. In contrast, TNF-α induced two enzymes (cyclooxygenase-2 and microsomal prostaglandin E synthase-1) that contribute to increased synthesis of PGE2. Overexpressing 15-PGDH blocked the increase in PGE2 production mediated by TNF-α. Taken together, these results suggest that reduced expression of 15-PGDH contributes to the elevated levels of PGE2 found in inflamed mucosa of IBD patients. The decrease in amounts of 15-PGDH in inflamed mucosa can be explained at least, in part, by TNF-α-mediated suppression of 15-PGDH transcription.

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IL-23/IL-17A Axis Correlates with the Nitric Oxide Pathway in Inflammatory Bowel Disease: Immunomodulatory Effect of Retinoic Acid

Journal of Interferon & Cytokine Research ◽

10.1089/jir.2012.0063 ◽

2013 ◽

Vol 33 (7) ◽

pp. 355-368 ◽

Cited By ~ 43

Author(s):

Hayet Rafa ◽

Houria Saoula ◽

Mourad Belkhelfa ◽

Oussama Medjeber ◽

Imene Soufli ◽

...

Keyword(s):

Nitric Oxide ◽

Inflammatory Bowel Disease ◽

Retinoic Acid ◽

Bowel Disease ◽

Immunomodulatory Effect ◽

Inflammatory Bowel ◽

Nitric Oxide Pathway

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Increased arginase activity and endothelial dysfunction in human inflammatory bowel disease

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00499.2006 ◽

2007 ◽

Vol 292 (5) ◽

pp. G1323-G1336 ◽

Cited By ~ 75

Author(s):

Scott Horowitz ◽

David G. Binion ◽

Victoria M. Nelson ◽

Yasmin Kanaa ◽

Pooria Javadi ◽

...

Keyword(s):

Nitric Oxide ◽

Ulcerative Colitis ◽

Inflammatory Bowel Disease ◽

Endothelial Cells ◽

Nitric Oxide Synthase ◽

Bowel Disease ◽

No Production ◽

Tnf Α ◽

Inflammatory Bowel ◽

Oxide Synthase

Nitric oxide (·NO) generation from conversion of l-arginine to citrulline by nitric oxide synthase isoforms plays a critical role in vascular homeostasis. Loss of ·NO is linked to vascular pathophysiology and is decreased in chronically inflamed gut blood vessels in inflammatory bowel disease (IBD; Crohn's disease and ulcerative colitis). Mechanisms underlying decreased ·NO production in IBD gut microvessels are not fully characterized. Loss of ·NO generation may result from increased arginase (AR) activity, which enzymatically competes with nitric oxide synthase for the common substrate l-arginine. We characterized AR expression in IBD microvessels and endothelial cells and its contribution to decreased ·NO production. AR expression was assessed in resected gut tissues and human intestinal microvascular endothelial cells (HIMEC). AR expression significantly increased in both ulcerative colitis and Crohn's disease microvessels and submucosal tissues compared with normal. TNF-α/lipopolysaccharide increased AR activity, mRNA and protein expression in HIMEC in a time-dependent fashion. RhoA/ROCK pathway, a negative regulator of ·NO generation in endothelial cells, was examined. The RhoA inhibitor C3 exoenzyme and the ROCK inhibitor Y-27632 both attenuated TNF-α/lipopolysaccharide-induced MAPK activation and blocked AR expression in HIMEC. A significantly higher AR activity and increased RhoA activity were observed in IBD submucosal tissues surrounding microvessels compared with normal control gut tissue. Functionally, inhibition of AR activity decreased leukocyte binding to HIMEC in an adhesion assay. Loss of ·NO production in IBD microvessels is linked to enhanced levels of AR in intestinal endothelial cells exposed to chronic inflammation in vivo.

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Cutaneous Manifestations in Biological-Treated Inflammatory Bowel Disease Patients: A Narrative Review

Journal of Clinical Medicine ◽

10.3390/jcm10051040 ◽

2021 ◽

Vol 10 (5) ◽

pp. 1040

Author(s):

Jo L. W. Lambert ◽

Sofie De Schepper ◽

Reinhart Speeckaert

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Cutaneous Manifestations ◽

Cutaneous Infections ◽

Tnf Α ◽

Common Skin ◽

Receptor Blockers ◽

Infusion Reactions ◽

Inflammatory Bowel ◽

Lichenoid Reactions

The biologic era has greatly improved the treatment of Crohn’s disease and ulcerative colitis. Biologics can however induce a wide variety of skin eruptions, especially those targeting the TNF-α and Th17 pathway. These include infusion reactions, eczema, psoriasis, lupus, alopecia areata, vitiligo, lichenoid reactions, granulomatous disorders, vasculitis, skin cancer, and cutaneous infections. It is important to recognize these conditions as treatment-induced adverse reactions and adapt the treatment strategy accordingly. Some conditions can be treated topically while others require cessation or switch of the biological therapy. TNF-α antagonists have the highest rate adverse skin eruptions followed by ustekinumab and anti-integrin receptor blockers. In this review, we provide an overview of the most common skin eruptions which can be encountered in clinical practice when treating IBD (Inflammatory bowel disease) patients and propose a therapeutic approach for each condition.

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Altered Leukotriene B4Metabolism in Colonic Mucosa with Inflammatory Bowel Disease

Scandinavian Journal of Gastroenterology ◽

10.3109/00365529509093234 ◽

1995 ◽

Vol 30 (1) ◽

pp. 44-49 ◽

Cited By ~ 16

Author(s):

A. Ikehata ◽

N. Hiwatashi ◽

Y. Kinouchi ◽

H. Yamazaki ◽

K. Ito ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Colonic Mucosa ◽

Inflammatory Bowel

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Myeloproliferative disorders in patients with inflammatory bowel disease on anti-TNF-α therapy

Inflammatory Bowel Diseases ◽

10.1002/ibd.21291 ◽

2011 ◽

Vol 17 (2) ◽

pp. 674-675 ◽

Cited By ~ 2

Author(s):

Monika Fischer ◽

Debra J. Helper ◽

Michael V. Chiorean

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Myeloproliferative Disorders ◽

Tnf Α ◽

Inflammatory Bowel

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Chronic Nonspecific Inflammatory Bowel Disease of the Cecum and Proximal Colon in Children With Grossly Normal-Appearing Colonic Mucosa: Diagnosis by Colonoscopic Biopsies

PEDIATRICS ◽

10.1542/peds.80.2.255 ◽

1987 ◽

Vol 80 (2) ◽

pp. 255-261

Author(s):

Melvin B. Heyman ◽

Jay A. Perman ◽

Linda D. Ferrell ◽

M. Michael Thaler

Keyword(s):

Inflammatory Bowel Disease ◽

Abdominal Pain ◽

Bowel Disease ◽

Colonic Mucosa ◽

Disease Process ◽

Proximal Colon ◽

Chronic Abdominal Pain ◽

Medical Attention ◽

Inflammatory Bowel ◽

Inflammatory Changes

The diagnosis of inflammatory bowel disease rests on radiologic, endoscopic, and histologic creteria. Five patients, 2 to 17 years of age, sought medical attention because of chronic abdominal pain, diarrhea, and heme-positive stools. Rectal biopsies, visual inspection of colonic mucosa through the colonoscope, and contrast radiographs of the large and small intestine yielded nonspecific results. Serial endoscopic biopsies demonstrated a gradient of inflammatory changes diminishing in severity distally from the ileocecal valve and cecum. The disease process was most evident in specimens from the cecum, whereas biopsies distal to the transverse colon had a normal histologic appearance in all five patients. Biopsies from the proximal colon may provide evidence of inflammatory bowel disease not detectable using standard techniques. The combination of chronic abdominal pain, diarrhea, and heme-positive stools associated with inflammatory changes in biopsy specimens obtained from the proximal colon, but normal findings on radiologic, colonoscopic, and rectal biopsy examinations, may represent an early stage in the evolution of chronic nonspecific inflammatory bowel disease, including ulcerative colitis or regional enteritis (Crohn disease).

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