Expression of hypoxia-inducible factor 1α in mononuclear phagocytes infected with Leishmania amazonensis

Degrossoli, Adriana; Bosetto, Maira Cegatti; Lima, Camila Bárbara Cantalupo; Giorgio, Selma

doi:10.1016/j.imlet.2007.09.009

Cited by 39 publications

(44 citation statements)

References 52 publications

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“…More interestingly, HIF1a and HIF-2a expressions occur earlier than the appearance of hypoxic areas in C57BL/6 footpad lesions, suggesting activation of HIFs independent of hypoxia. In fact, we and others have previously noted that HIFs expression could be independent of hypoxic stimuli [23,24,55]. In an in vitro system, L. amazonensis-infected macrophages express HIFs, although pimonidazole adducts are not found intracellularly; i.e., low oxygen tension (1-2 %) was not detected in cell cultures [23].…”

Section: Discussionmentioning

confidence: 76%

“…In fact, we and others have previously noted that HIFs expression could be independent of hypoxic stimuli [23,24,55]. In an in vitro system, L. amazonensis-infected macrophages express HIFs, although pimonidazole adducts are not found intracellularly; i.e., low oxygen tension (1-2 %) was not detected in cell cultures [23]. It should be noted that HIF1a is overexpressed in various tumor cells by hypoxiaindependent mechanisms [35].…”

Section: Discussionmentioning

confidence: 87%

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Immunohistochemical evidence of stress and inflammatory markers in mouse models of cutaneous leishmaniosis

Araújo

Giorgio

2015

Arch Dermatol Res

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Leishmanioses are chronic parasitic diseases and host responses are associated with pro- or anti-inflammatory cytokines involved, respectively, in the control or exacerbation of infection. The relevance of other inflammatory mediators and stress markers has not been widely studied and there is a need to search for biomarkers to leishmaniasis. In this work, the stress and inflammatory molecules p38 mitogen-activated protein kinase, cyclooxygenase-2, migration inhibitory factor, macrophage inflammatory protein 2, heat shock protein 70 kDa, vascular endothelial factor (VEGF), hypoxia-inducible factors (HIF-1α and HIF-2α), heme oxygenase and galectin-3 expression were assessed immunohistochemically in self-controlled lesions in C57BL/6 mice and severe lesions in Balb/c mice infected with Leishmania amazonensis. The results indicated that the majority of molecules were expressed in the cutaneous lesions of both C57BL/6 and Balb/c mice during various phases of infection, suggesting no obvious correlation between the stress and inflammatory molecule expression and the control/exacerbation of leishmanial lesions. However, the cytokine VEGF was only detected in C57BL/6 footpad lesions and small lesions in Balb/c mice treated with antimonial pentavalent. These findings suggest that VEGF expression could be a predictive factor for murine leishmanial control, a hypothesis that should be tested in human leishmaniosis.

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Section: Discussionmentioning

confidence: 76%

Section: Discussionmentioning

confidence: 87%

Immunohistochemical evidence of stress and inflammatory markers in mouse models of cutaneous leishmaniosis

Araújo

Giorgio

2015

Arch Dermatol Res

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“…For instance, the loss of myeloid cell HIF-1α renders mice more susceptible to many bacterial and viral pathogens [12,81,98]. In contrast, induction of HIF-1α is essential for the intracellular survival of some parasites [99][100][101]. this work it was shown that HIF-1α stabilization was essential for myeloid cell infiltration and activation in vivo.…”

Section: Hif-1α and Microbial Infectionsmentioning

confidence: 76%

“…In vitro studies reported the ability of both human and mouse mononuclear phagocytes and dendritic cells to stabilize HIF-1α after infection with L. amazonensis and L. donovani promastigotes [100,128]. The mechanism of HIF-1α stabilization relies on the impairment of PHD activity through alteration of the cellular iron pool.…”

Section: Hif-1α and Leishmaniamentioning

confidence: 99%

Hypoxia inducible factor 1α: A critical factor for the immune response to pathogens and Leishmania

Charpentier

Hammami

Stäger

2016

Cellular Immunology

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“…This factor is considered to be the main regulator of eukaryotic cells responses to physiological and hypoxic stress [16]. Recent studies showed that HIF-1α was expressed not only in hypoxic cells, but also in infection conditions [17] [18]. HIF-1α has been described to be expressed in hepatocytes under hypoxia or lipopolysaccharide (LPS) stimuli [19] [20].…”

Section: Introductionmentioning

confidence: 99%

Quantification of the Expression of HIF-1alpha by Real-Time PCR in Rat Hepatocytes Cultures Invaded by <i>Shigella flexneri</i> under Normoxic and Hypoxic Conditions

Lima¹,

Santos²,

Júnior³

2015

AiM

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Aim: Shigella flexneri (S. flexneri) is a gram-negative enterobacterium responsible for severe intestinal end systemic infection in humans. The bacteria can reach the liver due to degeneration of the colonic epithelium. Hypoxia is present in many human diseases and can induce the expression of the transcription factor HIF-1alpha that may have a cell protective role. The influence of hypoxia and HIF-1alpha on bacterial infection, studied in this work, is unclear. Hypoxia inducible factor1alpha (HIF-1alpha) is a transcription factor that acts as a master regulator of gene expression induced by hypoxia. Methods: We compared the ability of S. flexneri to invade rat hepatocytes in primary culture both in normoxic and hypoxic conditions. We evaluated TNF-alpha released by hepatocytes, apoptosis rate and HIF-1alpha expression by confocal microscopy as well as real time PCR technique. Results: We showed that S. flexneri invaded less hepatocytes previously submitted to 24 h hypoxia (6.5% O2) than those cultivated in normoxia (21% O2). S. flexneri also induced HIF-1α expression in hepatocytes, TNF-α secretion and apoptosis. Conclusion: a) Hypoxia alone was not a stimulus to TNF-α secretion, but induced cell apoptosis and HIF-1α expression; b) S. flexneri was able to invade rat hepatocytes and hypoxia apparently influenced significantly bacterial cell invasiveness; c) HIF-1α was expressed in hypoxic conditions, and it was also stimulated by S. flexneri.

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Expression of hypoxia-inducible factor 1α in mononuclear phagocytes infected with Leishmania amazonensis

Cited by 39 publications

References 52 publications

Immunohistochemical evidence of stress and inflammatory markers in mouse models of cutaneous leishmaniosis

Immunohistochemical evidence of stress and inflammatory markers in mouse models of cutaneous leishmaniosis

Hypoxia inducible factor 1α: A critical factor for the immune response to pathogens and Leishmania

Quantification of the Expression of HIF-1alpha by Real-Time PCR in Rat Hepatocytes Cultures Invaded by <i>Shigella flexneri</i> under Normoxic and Hypoxic Conditions

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Expression of hypoxia-inducible factor 1α in mononuclear phagocytes infected with Leishmania amazonensis

Cited by 39 publications

References 52 publications

Immunohistochemical evidence of stress and inflammatory markers in mouse models of cutaneous leishmaniosis

Immunohistochemical evidence of stress and inflammatory markers in mouse models of cutaneous leishmaniosis

Hypoxia inducible factor 1α: A critical factor for the immune response to pathogens and Leishmania

Quantification of the Expression of HIF-1alpha by Real-Time PCR in Rat Hepatocytes Cultures Invaded by &lt;i&gt;Shigella flexneri&lt;/i&gt; under Normoxic and Hypoxic Conditions

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Quantification of the Expression of HIF-1alpha by Real-Time PCR in Rat Hepatocytes Cultures Invaded by <i>Shigella flexneri</i> under Normoxic and Hypoxic Conditions