A reappraisal of the genomic organization of human Nox1 and its splice variants

Harper, Richart W; Xu, Changhong; Souček, Karel; Setiadi, Henny; Eiserich, Jason P.

doi:10.1016/j.abb.2004.12.021

Cited by 15 publications

(14 citation statements)

References 29 publications

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“…Increasing evidence has been reported to support the role of DUOX1 and DUOX2 in host defense against bacterial invasion at mucosal surfaces through the generation of H 2 O 2 [3,4]. While DUOX1 is induced following stimulation with IL-4 and IL-13, typical T helper (Th) 2 cytokines, DUOX2 is induced by the Th1 cytokine IFN-γ [5]. Additionally, DUOX2 is upregulated following infection with rhinovirus (RV) or Paramyxoviridae viruses, and in response to stimulation with polyinosinepolycytidylic acid (poly (I:C)), a synthetic double-stranded RNA analog [6,7].…”

Section: Introductionmentioning

confidence: 99%

IFNβ/TNFα synergism induces a non-canonical STAT2/IRF9-dependent pathway triggering a novel DUOX2 NADPH Oxidase-mediated airway antiviral response

et al. 2013

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Airway epithelial cells are key initial innate immune responders in the fight against respiratory viruses, primarily via the secretion of antiviral and proinflammatory cytokines that act in an autocrine/paracrine fashion to trigger the establishment of an antiviral state. It is currently thought that the early antiviral state in airway epithelial cells primarily relies on IFNβ secretion and the subsequent activation of the interferon-stimulated gene factor 3 (ISGF3) transcription factor complex, composed of STAT1, STAT2 and IRF9, which regulates the expression of a panoply of interferon-stimulated genes encoding proteins with antiviral activities. However, the specific pathways engaged by the synergistic action of different cytokines during viral infections, and the resulting physiological outcomes are still ill-defined. Here, we unveil a novel delayed antiviral response in the airways, which is initiated by the synergistic autocrine/paracrine action of IFNβ and TNFα, and signals through a non-canonical STAT2-and IRF9-dependent, but STAT1-independent cascade. This pathway ultimately leads to the late induction of the DUOX2 NADPH oxidase expression. Importantly, our study uncovers that the development of the antiviral state relies on DUOX2-dependent H 2 O 2 production. Key antiviral pathways are often targeted by evasion strategies evolved by various pathogenic viruses. In this regard, the importance of the novel DUOX2-dependent antiviral pathway is further underlined by the observation that the human respiratory syncytial virus is able to subvert DUOX2 induction.

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Section: Introductionmentioning

confidence: 99%

IFNβ/TNFα synergism induces a non-canonical STAT2/IRF9-dependent pathway triggering a novel DUOX2 NADPH Oxidase-mediated airway antiviral response

et al. 2013

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“…To explore potential mechanism(s) of IL-4-related tumor cell proliferation further, we examined the effect of IL-4 on the expression of the two known isoforms of NOX1, NOX1-L and NOX1-S [47]. Two sets of primers were used to detect these two distinct isoforms; NOX1-L is the full-length, functional form of NOX1, while NOX1-S is a smaller splice variant that lacks an NADPH binding site.…”

Section: Resultsmentioning

confidence: 99%

Interleukin-4 and interleukin-13 increase NADPH oxidase 1-related proliferation of human colon cancer cells

et al. 2017

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Human colon cancers express higher levels of NADPH oxidase 1 [NOX1] than adjacent normal epithelium. It has been suggested that reactive oxygen species [ROS] derived from NOX1 contribute to DNA damage and neoplastic transformation in the colon, particularly during chronic inflammatory stress. However, the mechanism(s) underlying increased NOX1 expression in malignant tumors or chronic inflammatory states involving the intestine are poorly characterized. We examined the effects of two pro-inflammatory cytokines, IL-4 and IL-13, on the regulation of NOX1. NOX1 expression was increased 4- to 5-fold in a time- and concentration-dependent manner by both cytokines in human colon cancer cell lines when a functional Type II IL-4 receptor was present. Increased NOX1 transcription following IL-4/IL-13 exposure was mediated by JAK1/STAT6 signaling, was associated with a ROS-related inhibition of protein tyrosine phosphatase activity, and was dependent upon activation and specific binding of GATA3 to the NOX1 promoter. NOX1-mediated ROS production increased cell cycle progression through S-phase leading to a significant increase in cellular proliferation. Evaluation of twenty pairs of surgically-resected colon cancers and their associated uninvolved adjacent colonic epithelium demonstrated a significant increase in the active form of NOX1, NOX1-L, in tumors compared to normal tissues, and a significant correlation between the expression levels of NOX1 and the Type II IL-4 receptor in tumor and the uninvolved colon. These studies imply that NOX1 expression, mediated by IL-4/IL-13, could contribute to an oxidant milieu capable of supporting the initiation or progression of colonic cancer, suggesting a role for NOX1 as a therapeutic target.

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“…NOX1 and NOX2 were found in total mRNA from prostate (55,353,454,841). NOX5 was described in prostate cancer cell lines and in prostatic adenocarcinomas (103).…”

Section: Prostatementioning

confidence: 99%

“…The existence of a second very short isoform of NOX1 had been suggested; however, this turned out to be an artifact due to the formation of a stable loop in the NOX1 mRNA (see Refs. 55,296,353). In mouse, several other splice variants due to the use of alternative promoters have been described (29).…”

Section: Nox1mentioning

confidence: 99%

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The NOX Family of ROS-Generating NADPH Oxidases: Physiology and Pathophysiology

Bedard¹,

Krause²

2007

Physiological Reviews

5,931

117

5,778

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For a long time, superoxide generation by an NADPH oxidase was considered as an oddity only found in professional phagocytes. Over the last years, six homologs of the cytochrome subunit of the phagocyte NADPH oxidase were found: NOX1, NOX3, NOX4, NOX5, DUOX1, and DUOX2. Together with the phagocyte NADPH oxidase itself (NOX2/gp91phox), the homologs are now referred to as the NOX family of NADPH oxidases. These enzymes share the capacity to transport electrons across the plasma membrane and to generate superoxide and other downstream reactive oxygen species (ROS). Activation mechanisms and tissue distribution of the different members of the family are markedly different. The physiological functions of NOX family enzymes include host defense, posttranlational processing of proteins, cellular signaling, regulation of gene expression, and cell differentiation. NOX enzymes also contribute to a wide range of pathological processes. NOX deficiency may lead to immunosuppresion, lack of otoconogenesis, or hypothyroidism. Increased NOX actvity also contributes to a large number or pathologies, in particular cardiovascular diseases and neurodegeneration. This review summarizes the current state of knowledge of the functions of NOX enzymes in physiology and pathology.

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A reappraisal of the genomic organization of human Nox1 and its splice variants

Cited by 15 publications

References 29 publications

IFNβ/TNFα synergism induces a non-canonical STAT2/IRF9-dependent pathway triggering a novel DUOX2 NADPH Oxidase-mediated airway antiviral response

IFNβ/TNFα synergism induces a non-canonical STAT2/IRF9-dependent pathway triggering a novel DUOX2 NADPH Oxidase-mediated airway antiviral response

Interleukin-4 and interleukin-13 increase NADPH oxidase 1-related proliferation of human colon cancer cells

The NOX Family of ROS-Generating NADPH Oxidases: Physiology and Pathophysiology

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