Abstract |
Nitric oxide (NO) plays an important role in the cutaneous response to UV radiation and in cutaneous inflammation. The presence of inducible NO synthase protein in a number of inflammatory dermatoses, coupled with the induction of an intense cutaneous inflammatory infiltrate following topical application of the NO donor-acidified nitrite (NO2(-)), has set the paradigm of NO being an inflammatory mediator in human skin. Using zeolite NO (Ze-NO), a chemically inert, pure NO donor, we have shown that NO per se produces little inflammation. Biologically, relevant doses of Ze-NO induce a dermal CD4-positive T-cell infiltrate and IFN-gamma secretion. In contrast acidified nitrite, releasing equal quantities of NO (measured by dermal microdialysis and cutaneous erythema), induces an intense epidermal infiltrate of macrophages with a similar dermal infiltrate of CD3-, CD4-, CD8-, and CD68-positive cells and neutrophils. Suction blisters were created in Ze-NO-treated and control skin. IFN-gamma, but not IL-4, was detected in Ze-NO-treated skin (mean control 0.1+/-0.07 pg mg(-1) protein, mean IFN-gamma 0.6+/-0.4 pg mg(-1) protein). We suggest that the potent inflammation induced by acidified NO2(-) is secondary to the release of additional mediators.
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Authors | Megan Mowbray, Xuejing Tan, Paul S Wheatley, Adriano G Rossi, Russell E Morris, Richard B Weller |
Journal | The Journal of investigative dermatology
(J Invest Dermatol)
Vol. 128
Issue 2
Pg. 352-60
(Feb 2008)
ISSN: 1523-1747 [Electronic] United States |
PMID | 17914444
(Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Acids
- Inflammation Mediators
- Nitric Oxide Donors
- Zeolites
- Nitric Oxide
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Topics |
- Acids
- Administration, Topical
- Blister
(chemically induced, immunology, pathology)
- Cell Movement
(drug effects, immunology)
- Dermatitis
(immunology, pathology, prevention & control)
- Edema
(chemically induced, immunology, pathology)
- Epidermis
(drug effects, immunology, pathology)
- Erythema
(chemically induced, immunology, pathology)
- Female
- Humans
- Inflammation Mediators
(administration & dosage, adverse effects)
- Langerhans Cells
(drug effects, pathology)
- Macrophages
(drug effects, pathology)
- Male
- Neutrophils
(drug effects, pathology)
- Nitric Oxide
(administration & dosage, adverse effects, immunology)
- Nitric Oxide Donors
(administration & dosage, adverse effects)
- Skin Ulcer
(chemically induced, immunology, pathology)
- T-Lymphocytes
(drug effects, pathology)
- Zeolites
(administration & dosage, adverse effects)
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