Inducible nitric oxide synthase (iNOS) and α-melanocyte-stimulating hormones of iNOS origin play important roles in the allergic reactions of atopic dermatitis in mice

Abstract

To elucidate the possible involvement of nitric oxide (NO) derived from inducible NO synthase (iNOS) in the pathogenesis of patients with allergic rhinitis, we used an animal model of atopic dermatitis (AD) induced by epicutaneous sensitization and analysed the differences in ear thickness, the frequency of scratching and plasma levels of ovalbumin-specific immunoglobulin E (OVA-IgE), transforming growth factor (TGF)-β, tumor necrosis factor (TNF)-α, adrenocorticotropic hormone (ACTH) and α-melanocyte-stimulating hormone (α-MSH) between control and iNOS(-/-) mice. Eight-week-old control and iNOS(-/-) male C57BL/6j mice were sensitized three times with OVA antigen. Before and after the last skin sensitization, the number of scratching incidents and the thickness of the ear were examined, and the plasma levels of OVA-IgE, α-MSH, ACTH, TGF-β and TNF-α were analysed by ELISA. Sensitization of mice with OVA resulted in increased plasma levels of OVA-IgE, α-MSH, ACTH, TGF-β and TNF-α in control, but not in iNOS(-/-) mice. The administration of l-nitro-arginine-methyl ester (l-NAME) abolished all the above changes that occurred in the control mice. In addition, iNOS(-/-) mice given α-MSH exhibited a change similar to that seen in the control, whereas iNOS(-/-) mice given ACTH, TGF-β or TNF-α did not demonstrate any changes. These results indicate that symptoms of AD such as scratching can be exacerbated by α-MSH, which is induced by iNOS-derived NO.

Arginase I levels are decreased in the plasma of pediatric patients with atopic dermatitis

“…In mouse models of AD-like lesions, skin showed increased iNOS expression and serum samples were noted to have increased nitrites compared to controls (14). Additionally, even after epicutaneous sensitization, iNOS knockout mice do not show the normally-induced symptoms of swelling/scratching, nor increased nitrite levels, as control mice show (15). More specifically to AD in humans, serum nitrate levels were found to be elevated in pediatric atopic dermatitis patients and were related to both severity of disease as well as eosinophil count (16).…”

The efficacy of whey associated with dodder seed extract on moderate-to-severe atopic dermatitis in adults: A randomized, double-blind, placebo-controlled clinical trial

“…In addition, the flavonoids quercetin and kaempferol show anti-inflammatory effects by modulating the pro-inflammatory factors, such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) (García-Mediavilla et al, 2007). Nitric oxide (NO) derived from inducible NO synthase (iNOS) is involved in the pathogenesis of allergic rhinitis and exacerbation of atopic dermatitis symptoms like scratching (Orita et al, 2011). Thus, it is concluded that consuming the aqueous extract of field dodder seeds can be helpful for the improvement of AD lesions due to decrease of inflammation.…”

Delineating the Role of Histamine-1- and -4-Receptors in a Mouse Model of Th2-Dependent Antigen-Specific Skin Inflammation

“…Imai et al describe increased blood histamine levels in transgenic mice spontaneously developing long-lasting dermatitis (by skin-specific IL-33 expression) [27], a phenotype which resembles the chronic phase of atopic dermatitis. Other groups could show elevated histamine levels in skin or serum only after repeated epicutaneous challenge [28], [29], suggesting that re-exposure might be necessary to induce measurable increases in histamine levels. It is thus conceivable that repeated patching could also lead to histamine increases in our model, a read-out parameter we did not address, though.…”