Protective role of heme oxygenase-1 in the intestinal tissue injury in an experimental model of sepsis

Fujii, Hiromi; Takahashi, Toru; Nakahira, Kiichi; Uehara, Kenji; Shimizu, Hiroko; Matsumi, Masaki; Morita, Kiyoshi; Hirakawa, Masahisa; Akagi, Reiko; Sassa, Shigeru

doi:10.1097/01.ccm.0000050442.54044.06

Cited by 67 publications

(50 citation statements)

References 33 publications

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“…Pathogen-associated molecular patterns (PAMPs) such as LPS, lipoteichoic acid, and peptidoglycan as well as several proinflammatory cytokines can induce HO-1 expression (41). The activation of HO-1 may thus act as an endogenous defensive mechanism to reduce inflammation and tissue injury in the intestinal tract (42)(43)(44) and may also be protective against lethal endotoxemia (45). HO-1 levels were significantly elevated in the systemic circulation in S. stercoralisinfected individuals in the present study.…”

Section: Discussionsupporting

confidence: 57%

Microbial Translocation Associated with an Acute-Phase Response and Elevations in MMP-1, HO-1, and Proinflammatory Cytokines in Strongyloides stercoralis Infection

et al. 2017

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Microbial translocation, characterized by elevated levels of lipopolysaccharide (LPS) and related markers, is a common occurrence in HIV and some parasitic infections. This is usually associated with extensive inflammation and immune activation. To examine the occurrence of microbial translocation and the associated inflammatory response in asymptomatic Strongyloides stercoralis infection, we measured the plasma levels of LPS and other microbial translocation markers, acutephase proteins, inflammatory markers, and proinflammatory cytokines in individuals with (infected [INF] . Following treatment of S. stercoralis infection, the elevated levels of microbial translocation markers, acute-phase proteins, and inflammatory markers were all diminished. Our data thus show that S. stercoralis infection is characterized by microbial translocation and accompanying increases in levels of acute-phase proteins and markers of inflammation and provide data to suggest that microbial translocation is a feature of asymptomatic S. stercoralis infection and is associated with an inflammatory response.KEYWORDS microbial translocation markers, Strongyloides stercoralis, acute-phase proteins, inflammatory markers, proinflammatory cytokines M icrobial translocation refers to the process by which the translocation of bacterial products results in elevated levels of lipopolysaccharide (LPS) in the circulation without overt bacteremia (1). LPS and 16S rRNA (common to most bacteria) are often used as indicators of bacterial translocation, and endotoxin core IgG antibody (EndoCAb) is also used as a surrogate marker for the measurement of circulating LPS levels (1, 2). iFABP may also reflect a breach in epithelial integrity associated with chronic intestinal infections (3). The prevalence of increased acute-phase protein concentrations during episodes of inflammation is used as a supporting prognostic and diag-

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Section: Discussionsupporting

confidence: 57%

Microbial Translocation Associated with an Acute-Phase Response and Elevations in MMP-1, HO-1, and Proinflammatory Cytokines in Strongyloides stercoralis Infection

et al. 2017

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“…LPS also increases HO-1 expression in vivo. In mice exposed to LPS, HO-1 is induced in various tissues, including liver, kidney, spleen, intestine, and peritoneal and tissue macrophages (45,46). In addition, HO-1-null mice exposed to endotoxin exhibit higher mortality rates and incidence of end-organ damage than wild-type littermates (18,19), suggesting that HO-1 plays a key role in protecting the host during sepsis.…”

Section: Discussionmentioning

confidence: 99%

Lipopolysaccharide-Induced Heme Oxygenase-1 Expression in Human Monocytic Cells Is Mediated via Nrf2 and Protein Kinase C

Rushworth

Chen²,

Mackman

et al. 2005

The Journal of Immunology

171

146

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Monocytes play a key role in mobilization of the immune response during sepsis. In response to LPS, monocytes produce both proinflammatory mediators and regulatory proteins that counteract the inflammation and oxidative stress. In murine macrophages, LPS stimulates expression of heme oxygenase 1 (HO-1), a cytoprotective enzyme that catalyzes the degradation of heme. The HO-1 5′-untranslated region, similarly to other cytoprotective genes, contains antioxidant-response elements (AREs) that can bind the transcription factor NF-E2-related factor 2 (Nrf2). At present, the role of Nrf2 in LPS-induced HO-1 expression in monocytic cells has not been investigated. In this study, LPS induced HO-1 mRNA and protein expression in human monocytes and THP-1 cells. Nrf2 translocated from the cytosol to the nucleus in response to LPS and bound to the ARE site in the human HO-1 promoter. In addition, a dominant negative Nrf2 mutant inhibited LPS-induced HO-1 mRNA expression but not TNF-α mRNA expression in THP-1 cells. Ro-31-8220, a pan-protein kinase C (PKC) inhibitor, and Go6976, a classical PKC inhibitor, blunted LPS-induced HO-1 mRNA expression in monocytes and THP-1 cells. Both PKC inhibitors also blocked LPS-induced Nrf2 binding to the ARE. These results indicate that LPS-induced HO-1 expression in human monocytic cells requires Nrf2 and PKC.

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“…Twenty micrograms of total RNA were subjected to electrophoresis in a 1.2% (w/v) agarose gel containing 6.5% (v/v) formaldehyde. After blotting on to a sheet of BIO-RAD Zeta-Probe TM membrane (Bio-Rad Laboratories, Richmond, CA), RNA samples were hybridized with [α-32 P] dCTP labeled cDNA probes for HO-1 [25] and TNF-α [26,27], respectively, followed by washing under stringent conditions. The membrane was exposed to a sheet of Fuji Medical radiograph film with an intensifying screen at -70°C, and autoradiographs and 18S ribosomal RNA were quantified by using an image scanner (GelPrint TM 2000i, Genomic Solutions, Ann…”

Section: Rna Isolation and Northern Blot Analysismentioning

confidence: 99%

Hemin Treatment Abrogates Monocrotaline-Induced Pulmonary Hypertension

Shimzu

Iwasaki

et al. 2008

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Treatment of rats with monocrotaline (MCT), a pyrrolizidine alkaloid plant toxin, is known to cause pulmonary hypertension (PH), and it has been used as a useful experimental model of PH. Recent findings suggested that pulmonary inflammation may play a significant role in the pathogenesis of MCT-induced PH. We also demonstrated that, following MCT administration to rats, there was a significant and sustained increase in the pulmonary expression of heme oxygenase-1 (HO-1), which is known to be induced by various oxidative stresses, including inflammation and free heme, and is thought to be essential in the protection against oxidative tissue injuries. In this study, we administered hemin (ferriprotoporphyrin chloride, 30 μmol/kg b.w., subcutaneously), a potent inducer of HO-1, every 3 days to rats following subcutaneous administration of MCT (60 mg/kg) and examined its effect on MCT-induced PH and pulmonary inflammation. MCT administration caused pulmonary arterial wall thickening with marked elevation of right ventricular pressure, in association with prominent pulmonary inflammation as revealed by the increase in gene expression of tumor necrosis factor-α and the number of infiltrated neutrophils in the lung. In contrast, hemin treatment of MCT-administered animals, which led to a further increase in pulmonary HO-1 mRNA expression, significantly ameliorated MCT-induced PH as well 3 as tissue inflammation. These findings suggest that hemin treatment ameliorates MCT-induced PH possibly mediated through induction of pulmonary HO-1 which leads to the attenuation of pulmonary inflammation.

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Protective role of heme oxygenase-1 in the intestinal tissue injury in an experimental model of sepsis

Cited by 67 publications

References 33 publications

Microbial Translocation Associated with an Acute-Phase Response and Elevations in MMP-1, HO-1, and Proinflammatory Cytokines in Strongyloides stercoralis Infection

Microbial Translocation Associated with an Acute-Phase Response and Elevations in MMP-1, HO-1, and Proinflammatory Cytokines in Strongyloides stercoralis Infection

Lipopolysaccharide-Induced Heme Oxygenase-1 Expression in Human Monocytic Cells Is Mediated via Nrf2 and Protein Kinase C

Hemin Treatment Abrogates Monocrotaline-Induced Pulmonary Hypertension

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