Regulation of tumor necrosis factor-α production in the isolated rat heart stimulated by bacterial lipopolysaccharide or reactive oxygen

G. Russell Jennings, Manuel R Castresana, Walter H. Newman

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Reperfusion after cardiopulmonary bypass causes induction of reactive oxygen species (ROS), elevated plasma levels of bacterial lipopolysaccharide (LPS), and production of tumor necrosis factor-α (TNF) by the heart. Nuclear factor-κB (NF-κB) regulates the expression of TNF. Because NF-κB is activated by both LPS and ROS, we hypothesized that an inhibitor of NF-κB, pyrrolidine dithiocarbamate (PDTC), would block release of TNF from the heart stimulated by these two agents. With Institutional animal care and use committee (IACUC) approval, rat hearts were perfused Langendorf style. LPS was infused and ROS were generated with a hypoxanthine/xanthine oxidase system. PDTC was added to the perfusion buffer. Other hearts were treated with forskolin in order to elevate cyclic AMP. Timed collections of coronary effluent were made for the determination of coronary flow and measurement of TNF. LPS stimulated TNF release to a maximum of 2247 ± 133 pg/min at 150 minutes. PDTC inhibited LPS-stimulated TNF release. For instance, at 150 minutes, LPS-stimulated TNF release was 449 ± 49 pg/min with 100 μM PDTC and was 70 ± 65 pg/mL with 250μM PDTC (P < 0.05 vs LPS alone). ROS stimulated TNF release was 1494 ± 130 pg/min at 150 minutes and was not affected by PDTC. Forskolin almost completely blocked TNF release stimulated by LPS or ROS. These data are consistent with the notion that inhibitors of NF-κB block cytokine production stimulated by some agents but not others.

Original languageEnglish (US)
Pages (from-to)797-800
Number of pages4
JournalAmerican Surgeon
Volume70
Issue number9
StatePublished - Dec 1 2004
Externally publishedYes

Fingerprint

Lipopolysaccharides
Tumor Necrosis Factor-alpha
Oxygen
Reactive Oxygen Species
Colforsin
Animal Care Committees
Xanthine Oxidase
Cardiopulmonary Bypass
Cyclic AMP
Reperfusion
pyrrolidine dithiocarbamic acid
Buffers
Perfusion
Cytokines

ASJC Scopus subject areas

  • Surgery

Cite this

Regulation of tumor necrosis factor-α production in the isolated rat heart stimulated by bacterial lipopolysaccharide or reactive oxygen. / Jennings, G. Russell; Castresana, Manuel R; Newman, Walter H.

In: American Surgeon, Vol. 70, No. 9, 01.12.2004, p. 797-800.

Research output: Contribution to journalArticle

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