Immunomodulatory effects of inhaled carbon monoxide on rat syngeneic small bowel graft motility

Atsunori Nakao, B. A. Moore, N. Murase, F. Liu, B. S. Zuckerbraun, F. H. Bach, A. M K Choi, M. A. Nalesnik, L. E. Otterbein, A. J. Bauer

Research output: Contribution to journalArticle

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Abstract

Background: Intestinal transplantation provokes an intense inflammatory response within the graft muscularis that causes intestinal ileus. We hypothesised that endogenously produced anti-inflammatory substances could be utilised as novel therapeutics. Therefore, we tested the protective effects of inhaled carbon monoxide (CO) and an endogenous haeme oxygenase 1 (HO-1) anti-inflammatory mediator on transplant induced inflammatory responses and intestinal ileus in the rat. Methods: Gastrointestinal transit of non-absorbable FITC labelled dextran and in vitro jejunal circular muscle contractions were measured in controls and syngeneic orthotopic transplanted animals with and without CO inhalation (250 ppm for 25 hours). Inflammatory mRNAs for interleukin (IL)-6, IL-1β, tumour necrosis factor α (TNF-α), intercellular adhesion molecule 1 (ICAM-1), inducible nitric oxide (iNOS), cyclooxygenase 2 (COX-2), and IL-10 were quantified by real time reverse transcriptase-polymerase chain reaction and HO-1 by northern blot. Histochemical stains characterised neutrophil infiltration and enterocyte apoptosis. Results: Transplantation delayed transit and suppressed jejunal circular muscle contractility. Transplantation induced dysmotility was significantly improved by CO inhalation. Transplantation initiated a significant upregulation in IL-6, IL- 1β, TNF-α, ICAM-1, iNOS, COX-2, and HO-1 mRNAs with the graft muscularis. CO inhalation significantly decreased expression of IL-6, IL-1β, iNOS, and COX-2 mRNAs. CO also significantly decreased serum nitrite levels (iNOS activity). Conclusions: CO inhalation significantly improved post-transplant motility and attenuated the inflammatory cytokine milieu in the syngeneic rat transplant model. Thus clinically providing CO, the end product of the anti-inflammatory HO-1 pathway, may prove to be an effective therapeutic adjunct for clinical small bowel transplantation.

Original languageEnglish
Pages (from-to)1278-1285
Number of pages8
JournalGut
Volume52
Issue number9
DOIs
Publication statusPublished - Sep 1 2003
Externally publishedYes

Fingerprint

Carbon Monoxide
Heme Oxygenase-1
Transplants
Transplantation
Inhalation
Cyclooxygenase 2
Interleukin-1
Interleukin-6
Anti-Inflammatory Agents
Ileus
Intercellular Adhesion Molecule-1
Messenger RNA
Gastrointestinal Transit
Neutrophil Infiltration
Enterocytes
Muscle Contraction
Nitrites
Reverse Transcriptase Polymerase Chain Reaction
Northern Blotting
Interleukin-10

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Nakao, A., Moore, B. A., Murase, N., Liu, F., Zuckerbraun, B. S., Bach, F. H., ... Bauer, A. J. (2003). Immunomodulatory effects of inhaled carbon monoxide on rat syngeneic small bowel graft motility. Gut, 52(9), 1278-1285. https://doi.org/10.1136/gut.52.9.1278

Immunomodulatory effects of inhaled carbon monoxide on rat syngeneic small bowel graft motility. / Nakao, Atsunori; Moore, B. A.; Murase, N.; Liu, F.; Zuckerbraun, B. S.; Bach, F. H.; Choi, A. M K; Nalesnik, M. A.; Otterbein, L. E.; Bauer, A. J.

In: Gut, Vol. 52, No. 9, 01.09.2003, p. 1278-1285.

Research output: Contribution to journalArticle

Nakao, A, Moore, BA, Murase, N, Liu, F, Zuckerbraun, BS, Bach, FH, Choi, AMK, Nalesnik, MA, Otterbein, LE & Bauer, AJ 2003, 'Immunomodulatory effects of inhaled carbon monoxide on rat syngeneic small bowel graft motility', Gut, vol. 52, no. 9, pp. 1278-1285. https://doi.org/10.1136/gut.52.9.1278
Nakao, Atsunori ; Moore, B. A. ; Murase, N. ; Liu, F. ; Zuckerbraun, B. S. ; Bach, F. H. ; Choi, A. M K ; Nalesnik, M. A. ; Otterbein, L. E. ; Bauer, A. J. / Immunomodulatory effects of inhaled carbon monoxide on rat syngeneic small bowel graft motility. In: Gut. 2003 ; Vol. 52, No. 9. pp. 1278-1285.
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abstract = "Background: Intestinal transplantation provokes an intense inflammatory response within the graft muscularis that causes intestinal ileus. We hypothesised that endogenously produced anti-inflammatory substances could be utilised as novel therapeutics. Therefore, we tested the protective effects of inhaled carbon monoxide (CO) and an endogenous haeme oxygenase 1 (HO-1) anti-inflammatory mediator on transplant induced inflammatory responses and intestinal ileus in the rat. Methods: Gastrointestinal transit of non-absorbable FITC labelled dextran and in vitro jejunal circular muscle contractions were measured in controls and syngeneic orthotopic transplanted animals with and without CO inhalation (250 ppm for 25 hours). Inflammatory mRNAs for interleukin (IL)-6, IL-1β, tumour necrosis factor α (TNF-α), intercellular adhesion molecule 1 (ICAM-1), inducible nitric oxide (iNOS), cyclooxygenase 2 (COX-2), and IL-10 were quantified by real time reverse transcriptase-polymerase chain reaction and HO-1 by northern blot. Histochemical stains characterised neutrophil infiltration and enterocyte apoptosis. Results: Transplantation delayed transit and suppressed jejunal circular muscle contractility. Transplantation induced dysmotility was significantly improved by CO inhalation. Transplantation initiated a significant upregulation in IL-6, IL- 1β, TNF-α, ICAM-1, iNOS, COX-2, and HO-1 mRNAs with the graft muscularis. CO inhalation significantly decreased expression of IL-6, IL-1β, iNOS, and COX-2 mRNAs. CO also significantly decreased serum nitrite levels (iNOS activity). Conclusions: CO inhalation significantly improved post-transplant motility and attenuated the inflammatory cytokine milieu in the syngeneic rat transplant model. Thus clinically providing CO, the end product of the anti-inflammatory HO-1 pathway, may prove to be an effective therapeutic adjunct for clinical small bowel transplantation.",
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AU - Nakao, Atsunori

AU - Moore, B. A.

AU - Murase, N.

AU - Liu, F.

AU - Zuckerbraun, B. S.

AU - Bach, F. H.

AU - Choi, A. M K

AU - Nalesnik, M. A.

AU - Otterbein, L. E.

AU - Bauer, A. J.

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N2 - Background: Intestinal transplantation provokes an intense inflammatory response within the graft muscularis that causes intestinal ileus. We hypothesised that endogenously produced anti-inflammatory substances could be utilised as novel therapeutics. Therefore, we tested the protective effects of inhaled carbon monoxide (CO) and an endogenous haeme oxygenase 1 (HO-1) anti-inflammatory mediator on transplant induced inflammatory responses and intestinal ileus in the rat. Methods: Gastrointestinal transit of non-absorbable FITC labelled dextran and in vitro jejunal circular muscle contractions were measured in controls and syngeneic orthotopic transplanted animals with and without CO inhalation (250 ppm for 25 hours). Inflammatory mRNAs for interleukin (IL)-6, IL-1β, tumour necrosis factor α (TNF-α), intercellular adhesion molecule 1 (ICAM-1), inducible nitric oxide (iNOS), cyclooxygenase 2 (COX-2), and IL-10 were quantified by real time reverse transcriptase-polymerase chain reaction and HO-1 by northern blot. Histochemical stains characterised neutrophil infiltration and enterocyte apoptosis. Results: Transplantation delayed transit and suppressed jejunal circular muscle contractility. Transplantation induced dysmotility was significantly improved by CO inhalation. Transplantation initiated a significant upregulation in IL-6, IL- 1β, TNF-α, ICAM-1, iNOS, COX-2, and HO-1 mRNAs with the graft muscularis. CO inhalation significantly decreased expression of IL-6, IL-1β, iNOS, and COX-2 mRNAs. CO also significantly decreased serum nitrite levels (iNOS activity). Conclusions: CO inhalation significantly improved post-transplant motility and attenuated the inflammatory cytokine milieu in the syngeneic rat transplant model. Thus clinically providing CO, the end product of the anti-inflammatory HO-1 pathway, may prove to be an effective therapeutic adjunct for clinical small bowel transplantation.

AB - Background: Intestinal transplantation provokes an intense inflammatory response within the graft muscularis that causes intestinal ileus. We hypothesised that endogenously produced anti-inflammatory substances could be utilised as novel therapeutics. Therefore, we tested the protective effects of inhaled carbon monoxide (CO) and an endogenous haeme oxygenase 1 (HO-1) anti-inflammatory mediator on transplant induced inflammatory responses and intestinal ileus in the rat. Methods: Gastrointestinal transit of non-absorbable FITC labelled dextran and in vitro jejunal circular muscle contractions were measured in controls and syngeneic orthotopic transplanted animals with and without CO inhalation (250 ppm for 25 hours). Inflammatory mRNAs for interleukin (IL)-6, IL-1β, tumour necrosis factor α (TNF-α), intercellular adhesion molecule 1 (ICAM-1), inducible nitric oxide (iNOS), cyclooxygenase 2 (COX-2), and IL-10 were quantified by real time reverse transcriptase-polymerase chain reaction and HO-1 by northern blot. Histochemical stains characterised neutrophil infiltration and enterocyte apoptosis. Results: Transplantation delayed transit and suppressed jejunal circular muscle contractility. Transplantation induced dysmotility was significantly improved by CO inhalation. Transplantation initiated a significant upregulation in IL-6, IL- 1β, TNF-α, ICAM-1, iNOS, COX-2, and HO-1 mRNAs with the graft muscularis. CO inhalation significantly decreased expression of IL-6, IL-1β, iNOS, and COX-2 mRNAs. CO also significantly decreased serum nitrite levels (iNOS activity). Conclusions: CO inhalation significantly improved post-transplant motility and attenuated the inflammatory cytokine milieu in the syngeneic rat transplant model. Thus clinically providing CO, the end product of the anti-inflammatory HO-1 pathway, may prove to be an effective therapeutic adjunct for clinical small bowel transplantation.

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