UVB Radiation-Mediated Expression of Inducible Nitric Oxide Synthase Activity and the Augmenting Role of Co-Induced TNF-α in Human Skin Endothelial Cells

Abstract

Nitric oxide (NO) plays a pivotal role in ultraviolet radiation-induced inflammation in human skin. We had earlier reported on the inducible nitric oxide synthase (iNOS) inducing activity of UVA radiation. We now demonstrate that UVB-exposure induces expression of the iNOS in vessel endothelia of normal human skin and in cultured human dermal endothelial cells (HUDEC), although by a molecular mechanism different from UVA-mediated induction. With HUDEC, UVB induces iNOS expression and leads to significant enzyme activities, although at app. 5-fold lower levels than can be achieved with proinflammatory cytokines. In contrast to our earlier observation with UVA, cytokine-challenge combined with simultaneous UVB-exposure had no additive effects on iNOS expression nor activity. Interestingly, a time-delay between UVB-irradiation and cytokine-challenge enhances endothelial iNOS enzyme activity 2.5-fold over cytokines activation only. This time-dependent effect strongly correlates with UVB-induced endothelial TNF-alpha expression. In HUDEC addition of TNF-alpha results in enhanced expression of the inducible arginine transporter system CAT-2 essential for substrate supply and thus iNOS activity. In summary, UVB induces iNOS mRNA and enzyme activity in HUDEC. Moreover, UVB augments CAT-2 expression through a TNF-alpha- dependent mechanism which essentially contributes to increased iNOS activity.

Ferulic acid inhibits UVB-radiation induced photocarcinogenesis through modulating inflammatory and apoptotic signaling in Swiss albino mice

“…Prolonged exposure of the human skin to UVB can result in inflammation including erythema, edema formation, premature aging, immunesuppression and skin cancer (Matsumura and Ananthaswamy, 2004;Heck et al, expression of the iNOS in vessel endothelia of normal human skin (Suschek et al, 2004).…”

Anti-inflammatory and ECM gene expression modulations of β-eudesmol via NF-κB signaling pathway in normal human dermal fibroblasts

“…Transcription of gene expression within which these molecules are coded is controlled by NF-κB (Gloire et al 2006). Through intracellular signal transmission, NF-κB controls various cell metabolism, but in that case, it works as transcription factor of inflammation-mediated substances and it promotes transcription of COX2, Eselectin, inducible nitric oxide synthase (iNOS), intercellular adhesion molecule-1 (ICAM-1), IL-6, IL-12, IL-1β, MMP, TNF-α, and vascular cell adhesion molecular 1 (VCAM-1) to accelerate inflammation reaction and cause tissue damage (Limuro et al 1997;Bukman et al 1998;Chen et al 1999;Suschek et al 2004;Yamamoto and Gaynor 2001;Farooqui et al 2007).…”

In Vivo Nitric Oxide Production and iNOS Expression in X-Ray Irradiated Mouse Skin

“…4) In fact, UV radiation-mediated expression of inducible nitric oxide synthase (iNOS) was reported in the vessel endothelia of normal human skin and in cultured human dermal endothelial cells. 5) iNOS has been implicated in the pathogeneses of various inflammatory syndromes, including asthma, 6) transplant rejection, 7) inflammatory bowel disease, 8) rheumatoid arthritis, 9) septic shock 10) and parasitic infections.11) The expression of iNOS is also strongly implicated in psoriasis 12) and other inflammatory skin conditions including UV irradiation as stated above.5) Reactive oxygen species (ROS) have been connected with the pathogenesis of both inflammation syndromes 13) and UV-caused skin damage. 14) Similarly, the predominant event for ionizing irradiation of cell and tissue is the generation of ROS, for example, hydroxyl radicals and superoxide anion.…”

“…4) In fact, UV radiation-mediated expression of inducible nitric oxide synthase (iNOS) was reported in the vessel endothelia of normal human skin and in cultured human dermal endothelial cells. 5) iNOS has been implicated in the pathogeneses of various inflammatory syndromes, including asthma, 6) transplant rejection, 7) inflammatory bowel disease, 8) rheumatoid arthritis, 9) septic shock 10) and parasitic infections. 11) The expression of iNOS is also strongly implicated in psoriasis 12) and other inflammatory skin conditions including UV irradiation as stated above.…”

“…11) The expression of iNOS is also strongly implicated in psoriasis 12) and other inflammatory skin conditions including UV irradiation as stated above. 5) Reactive oxygen species (ROS) have been connected with the pathogenesis of both inflammation syndromes 13) and UV-caused skin damage. 14) Similarly, the predominant event for ionizing irradiation of cell and tissue is the generation of ROS, for example, hydroxyl radicals and superoxide anion.…”