Heme Oxygenase-1 Expression in Human Lungs with Cystic Fibrosis and Cytoprotective Effects against <i>Pseudomonas Aeruginosa In Vitro</i>

Zhou, Hailan; Lu, Fuhua; Latham, Christopher; Zander, Dani S.; Visner, Gary

doi:10.1164/rccm.200311-1607oc

Cited by 72 publications

(55 citation statements)

References 50 publications

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“…In asthmatic patients, exhaled CO and sputum bilirubin levels have been shown to be elevated in agreement with increased HO-1 staining [15,38]. Increased ferritin staining in AMs was observed in cystic fibrosis lungs compared with normal lungs, and the number of ferritin-stained macrophages correlated with the amount of HO-1 staining [17]. Inhaled CO had suppressive effects on fibrosis in bleomycin models of lung injury [39].…”

Section: Discussionmentioning

confidence: 86%

“…HO-1 has been implicated in a number of conditions and diseases associated with lung injury. HO-1 seems to be upregulated in smokers, asthma, acute lung injury, cystic fibrosis and lung transplant rejection, whereas it is downregulated in severe chronic obstructive pulmonary disease [14][15][16][17][18][19]. Since an oxidantantioxidant imbalance contributes to the pathogenesis of lung fibrosis, HO-1, one of the critical defenders against oxidative stress, may be important in fibrotic lung diseases.…”

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confidence: 99%

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Decreased expression of haem oxygenase-1 by alveolar macrophages in idiopathic pulmonary fibrosis

Dalavanga²,

Poulakis³

et al. 2008

Eur Respir J

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Haem oxygenase (HO)-1 is an oxidative stress responsive protein that may be involved in the pathogenesis of interstitial lung disease.HO-1 expression in alveolar macrophages from bronchoalveolar lavage was investigated in 24 patients with idiopathic pulmonary fibrosis (IPF), 16 with sarcoidosis, 14 with hypersensitivity pneumonitis (HP) and 13 controls. Using immunocytochemistry, HO-1 expression in macrophages was scored semiquantitatively from 0-3 according to increasing intensity. The mean score of 100 macrophages was calculated. Macrophages were cultured and levels of interleukin (IL)-12 and IL-18 in the culture supernatants were measured by ELISA.The mean score of HO-1 was significantly lower in IPF (67) than in sarcoidosis (105), HP (106) or controls (106). There was no significant difference between sarcoidosis, HP and controls. The score of HO-1 correlated positively with the lymphocyte percentage in sarcoidosis and HP. Positive correlations were found between the score of HO-1 and the release of IL-12 and IL-18 by macrophages in IPF.The expression of haem oxygenase-1, a critical defender against oxidative stress, is decreased in macrophages of idiopathic pulmonary fibrosis patients compared with those with granulomatous lung disorders. This supports the hypothesis of an oxidant-antioxidant imbalance in the pathogenesis of idiopathic pulmonary fibrosis.

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Section: Discussionmentioning

confidence: 86%

mentioning

confidence: 99%

Decreased expression of haem oxygenase-1 by alveolar macrophages in idiopathic pulmonary fibrosis

Dalavanga²,

Poulakis³

et al. 2008

Eur Respir J

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“…17,18,57,58 Indeed, the levels of human HO-1 in the lungs of P. aeruginosa infected CF patients have been shown to be up-regulated in a cytoprotective response to bacterial induced oxidative stress and inflammation, highlighting the host's response in restricting access of the pathogen to heme. 59 Therefore, by effectively eliminating or restricting the ability of the pathogen to acquire and utilize heme, we would expect to see significant reduction in the virulence of the organism.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of the Bacterial Heme Oxygenases from Pseudomonas aeruginosa and Neisseria meningitidis: Novel Antimicrobial Targets

et al. 2007

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The final step in heme utilization and iron acquisition in many pathogens is the oxidative cleavage of heme by heme oxygenase (HO), yielding iron, biliverdin, and carbon monoxide. Thus, the essential requirement for iron suggests that HO may provide a potential therapeutic target for antimicrobial drug development. Computer-aided drug design (CADD) combined with experimental assays identified small-molecule inhibitors of the Neisseria meningitidis HO (nm-HO). CADD virtual screening applied to 800 000 compounds identified 153 for biological assay. Several of the compounds were shown to have K D values in the micromolar range for nm-HO and the Pseudomonas aeruginosa HO (pa-HO). The compounds also inhibited the growth of P. aeruginosa as well as biliverdin formation in E. coli cells overexpressing nm-HO. Thus, CADD combined with experimental analysis has been used to identify novel inhibitors of the bacterial heme oxygenases that can cross the cell membrane and specifically inhibit HO activity.

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“…In cultured murine fibroblasts, regulated overexpression of HO-1 conferred protection against tumor necrosis factor (TNF)-α -mediated apoptosis (96). Finally, in a human respiratory epithelial cell line representative of lung epithelial cells found in patients with cystic fibrosis, overexpression of HO-1 conferred protection against Pseudomonas-mediated cellular injury and apoptosis (97).…”

Section: Hsp 32 (Heme Oxygenase)mentioning

confidence: 99%

Heat shock response and acute lung injury☆

Wheeler

Wong

2007

Free Radical Biology and Medicine

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All cells respond to stress through the activation of primitive, evolutionarily conserved genetic programs that maintain homeostasis and assure cell survival. Stress adaptation, which is known in the literature by a myriad of terms, including tolerance, desensitization, conditioning, and reprogramming, is a common paradigm found throughout nature, in which a primary exposure of a cell or organism to a stressful stimulus (e.g., heat) results in an adaptive response by which a second exposure to the same stimulus produces a minimal response. More interesting is the phenomenon of cross-tolerance, by which a primary exposure to a stressful stimulus results in an adaptive response whereby the cell or organism is resistant to a subsequent stress that is different from the initial stress (i.e. exposure to heat stress leading to resistance to oxidant stress). The heat shock response is one of the more commonly described examples of stress adaptation and is characterized by the rapid expression of a unique group of proteins collectively known as heat shock proteins (also commonly referred to as stress proteins). The expression of heat shock proteins is well described in both whole lungs and in specific lung cells from a variety of species and in response to a variety of stressors. More importantly, in vitro data, as well as data from various animal models of acute lung injury, demonstrate that heat shock proteins, especially Hsp27, Hsp32, Hsp60, and Hsp70 have an important cytoprotective role during lung inflammation and injury.

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Heme Oxygenase-1 Expression in Human Lungs with Cystic Fibrosis and Cytoprotective Effects against Pseudomonas Aeruginosa In Vitro

Cited by 72 publications

References 50 publications

Decreased expression of haem oxygenase-1 by alveolar macrophages in idiopathic pulmonary fibrosis

Decreased expression of haem oxygenase-1 by alveolar macrophages in idiopathic pulmonary fibrosis

Inhibition of the Bacterial Heme Oxygenases from Pseudomonas aeruginosa and Neisseria meningitidis: Novel Antimicrobial Targets

Heat shock response and acute lung injury☆

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