Role of Nitric Oxide in Chronic Allergen-Induced Airway Cell Proliferation and Inflammation

Eynott, Paul R.; Paavolainen, Niko; Groneberg, David A.; Noble, Alistair; Salmon, M; Nath, Puneeta; Leung, Suet Yi; Chung, Kian Fan

doi:10.1124/jpet.102.040295

Cited by 55 publications

(30 citation statements)

References 38 publications

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“…While the function of iNOS in the process of airway inflammation has been addressed in a number of reports [31][32][33][34], its exact role remains elusive. This is due primarily to the different roles that its product (NO) plays during inflammation.…”

Section: Discussionmentioning

confidence: 99%

Reciprocal regulation of iNOS and PARP-1 during allergen-induced eosinophilia

Naura

Datta²,

Hans³

et al. 2008

Eur Respir J

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Inducible nitric oxide synthase (iNOS) inhibition was recently shown to exert no effect on allergen challenge in human asthma, raising serious concerns about the role of the protein in the disease. The present study investigated the role of iNOS in ovalbumin-induced eosinophilia from the perspective of its relationship with poly(ADP-ribose) polymerase-1 (PARP-1) and oxidative DNA damage.A mouse model of ovalbumin-induced eosinophilia was used to conduct the studies. iNOS-associated protein nitration and tissue damage were partially responsible for allergeninduced eosinophilia. iNOS expression was required for oxidative DNA damage and PARP-1 activation upon allergen challenge. PARP-1 was required for iNOS expression and protein nitration, and this requirement was connected to nuclear factor-kB. PARP-1 was an important substrate for iNOS-associated by-products after ovalbumin-challenge. PARP-1 nitration blocked its poly(ADPribosyl)ation activity. Interleukin-5 re-establishment in ovalbumin-exposed PARP-1 -/-mice reversed eosinophilia and partial mucus production without a reversal of iNOS expression, concomitant protein nitration or associated DNA damage.The present results demonstrate a reciprocal relationship between inducible nitric oxide synthase and poly(ADP-ribose) polymerase-1 and suggest that expression of inducible nitric oxide synthase may be dispensable for eosinophilia after interleukin-5 production. Inducible nitric oxide synthase may be required for oxidative DNA damage and full manifestation of mucus production. Such dispensability may explain, in part, the reported ineffectiveness of inducible nitric oxide synthase inhibition in preventing allergen-induced inflammation in humans.

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Section: Discussionmentioning

confidence: 99%

Reciprocal regulation of iNOS and PARP-1 during allergen-induced eosinophilia

Naura

Datta²,

Hans³

et al. 2008

Eur Respir J

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“…Also, the role of nitric oxide, a previously characterized mediator of allergic airway inflammation (45,46) was studied in a guinea-pig of allergic conjunctivitis and a series of experiments demonstrated a major role of this gaseous molecule in regulating the vascular permeability and stimulating prostaglandin E2 production (47,48). As with other species, some guinea-pig strains may be more subtle to allergen sensitization and challenge.…”

Section: Guinea-pigsmentioning

confidence: 99%

“…All major laboratory rat strains have been used to establish allergic conjunctivitis models. Next to Brown-Norway rats (60,61), which are also the preferred strain for the induction of allergic airway inflammation (45,46) IgE-mediated models. IgE-mediated models of rat conjunctivitis used either direct or indirect sensitization and a large number of questions were answered with this species.…”

Section: Ratsmentioning

confidence: 99%

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Animal models of allergic and inflammatory conjunctivitis

Groneberg

Bielory

Fischer

et al. 2003

Allergy

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Numerous recent reports have demonstrated an increase in the prevalence and incidence of allergic conditions during the past years which affect approximately 25% of the general population (1) and about US$ 6 billion alone are estimated as direct costs of allergic rhinoconjunctivitis (2). Whereas a large amount of studies have focused on the pathophysiology of allergic rhinitis and asthma over the past years, ocular allergies are less well studied. However, allergic diseases affecting the eye are very common (3) and pediatric studies have shown that within distinct cohorts, up to 32% of allergic children have an ocular allergy as the primary manifestation of allergy (4). Allergic eye diseases such as allergic conjunctivitis commonly present with the symptoms of itchy, watery, red, sore and swollen eyes, but not pain (5).In contrast to the large amount of experimental studies on allergic asthma and the detailed knowledge that exists on mediators of allergic airway inflammation (6-8), there are few experimental studies using models of allergic eye diseases. Detailed reviews to assess the pathophysiology and immunology of ocular allergies have been limited. This review hopefully fills this void to provide the clinical and translational researcher in the area of ocular allergy. Pathophysiology of ocular allergiesBefore characterizing the different animal models of ocular allergy which have been established so far, it is crucial to reflect that within the area of ocular allergies, different disease entities exist and that only some of them may be mimicked by animal models. Formally, conjunctivitis may be divided into allergic and nonallergic conjunctivitis and the allergic form may also be subdivided into IgE-mediated and non-IgE-mediated allergic conjunctivitis ( Fig. 1) (9). Clinically, the spectrum of conjunctivitis types can be subdivided into allergic conjunctivitis, atopic keratoconjunctivitis, vernal keratoconjunctivitis and giant papillary conjunctivitis.In contrast to the other forms of conjunctivitis, allergic conjunctivitis is commonly based on an IgEmediated hypersensitivity reaction. Furthermore, allergic Allergic eye diseases are complex inflammatory conditions of the conjunctiva with an increasing prevalence and incidence. The diseases are often concomitant with other allergic diseases such as allergic rhinitis, atopic dermatitis and allergic asthma. Despite the disabling and prominent symptoms of ocular allergies, they are less well studied and further insights into the molecular basics are still required. To establish new therapeutic approaches and assess immunological mechanisms, animal models of ocular allergies have been developed in the past years. The major forms of allergic ocular diseases, seasonal and perennial allergic conjunctivitis, vernal and atopic keratoconjunctivitis and giant papillary conjunctivitis, each have different pathophysiological and immunological components. In contrast to these distinct entities, the current animal models are based on the sensitization against a small numbe...

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“…These interactions are orchestrated by a large number of neuromediators such as tachykinins (6), CGRP, vasoactive intestinal polypeptide (VIP), gaseous molecules such as nitric oxide or carbon monoxide (7,8) or endogenous opioids.…”

mentioning

confidence: 99%

Neurogenic mechanisms in bronchial inflammatory diseases

Groneberg

Quarcoo

Frossard

et al. 2004

Allergy

153

103

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Neurogenic inflammation encompasses the release of neuropeptides from airway nerves leading to inflammatory effects. This neurogenic inflammatory response of the airways can be initiated by exogenous irritants such as cigarette smoke or gases and is characterized by a bi‐directional linkage between airway nerves and airway inflammation. The event of neurogenic inflammation may participate in the development and progression of chronic inflammatory airway diseases such as allergic asthma or chronic obstructive pulmonary disease (COPD). The molecular mechanisms underlying neurogenic inflammation are orchestrated by a large number of neuropeptides including tachykinins such as substance P and neurokinin A, or calcitonin gene‐related peptide. Also, other biologically active peptides such as neuropeptide tyrosine, vasoactive intestinal polypeptide or endogenous opioids may modulate the inflammatory response and recently, novel tachykinins such as virokinin and hemokinins were identified. Whereas the different aspects of neurogenic inflammation have been studied in detail in laboratory animal models, only little is known about the role of airway neurogenic inflammation in human diseases. However, different functional properties of airway nerves may be used as targets for future therapeutic strategies and recent clinical data indicates that novel dual receptor antagonists may be relevant new drugs for bronchial asthma or COPD.

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Role of Nitric Oxide in Chronic Allergen-Induced Airway Cell Proliferation and Inflammation

Cited by 55 publications

References 38 publications

Reciprocal regulation of iNOS and PARP-1 during allergen-induced eosinophilia

Reciprocal regulation of iNOS and PARP-1 during allergen-induced eosinophilia

Animal models of allergic and inflammatory conjunctivitis

Neurogenic mechanisms in bronchial inflammatory diseases

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