title: Divergent effects of ischemia/reperfusion and nitric oxide donor on TNFalpha mRNA accumulation in rat organs.
abstract: We previously showed that serum TNFalpha bioactivity in rats is proportional to the extent of graded tissue injury caused by laparotomy, intestinal ischemia, and reperfusion and that the spleen is an important source of TNFalpha secretion in this condition. TNFalpha production varies, depending on the type and duration of tissue injury. It is also affected by other mediators, such as nitric oxide (NO). TNFalpha is known to increase NO production, but the effect of NO on the production of TNFalpha has not yet been fully elucidated. In this study we determined the levels of TNFalpha mRNA in rat organs after graded injury caused by anesthesia, laparotomy, intestinal ischemia, and reperfusion and evaluated the effects of the NO donor S-nitroso-N-acetylpenicillamine (SNAP) on it. Samples from different organs were removed, and TNFalpha gene expression was evaluated by semiquantitative RT-PCR. TNFalpha mRNA was not detected in the intestine (the ischemic organ) and in the kidney, brain, heart, or liver after all 4 experimental protocols. In the mesenteric lymph node (draining the ischemic organ) a basal level of expression of TNFalpha mRNA was detected in the control (anesthesia alone) group, which was increased significantly after ischemia. In the spleen (a remote immune organ not directly involved in the ischemia), a significant gradual increase in TNFalpha mRNA, which correlated to the severity of the experimental protocol, was observed. In the lung (a central participant in post-injury multiple organ failure), all interventions increased TNFalpha mRNA. Infusion of SNAP exerted a differential effect on TNFalpha mRNA: diminished its accumulation in the lymph node, enhanced it in the lung, and had no effect in the spleen. The divergent organ pattern of TNFalpha transcription emphasizes the importance of its localized expression, which is critical to the understanding of its autocrine and paracrine actions in ischemia and reperfusion.
authors: Immunology Research Unit, Lady Davis Carmel Medical Center, Rappaport Family Institute for Research in the Medical Sciences, Faculty of Medicine, Technion-Israel Institute of Technology, Haifa.
authors: M A
authors: MA
authors: Rahat
authors: N
authors: N
authors: Lahat
authors: J
authors: J
authors: Smollar
authors: V
authors: V
authors: Brod
authors: A
authors: A
authors: Kinarty
authors: H
authors: H
authors: Bitterman
mesh_terms: D000768:Anesthesia, General / Q000009:adverse effects; D000818:Animals; D018988:Bacterial Translocation; D001794:Blood Pressure; D001921:Brain / Q000378:metabolism / Q000473:pathology; D003250:Constriction; D005786:Gene Expression Regulation; D006400:Hematocrit; D006863:Hydrogen-Ion Concentration; D007422:Intestines / Q000098:blood supply*; D007511:Ischemia / Q000378:metabolism* / Q000473:pathology; D007773:Lactates / Q000097:blood; D007813:Laparotomy / Q000009:adverse effects*; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D008297:Male; D017538:Mesenteric Artery, Superior; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D020030:Nitric Oxide Donors / Q000494:pharmacology* / Q000627:therapeutic use; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D009928:Organ Specificity; D018384:Oxidative Stress; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000627:therapeutic use; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology; D013152:Splanchnic Circulation; D013154:Spleen / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D007773:Lactates; D020030:Nitric Oxide Donors; D012333:RNA, Messenger; C110881:S-nitro-N-acetylpenicillamine; D014409:Tumor Necrosis Factor-alpha; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D010396:Penicillamine