title: Intercellular pathway through hyaluronic acid in UVB-induced inflammation.
abstract: Ultraviolet B (UVB) radiation induces inflammation in the skin specifically at the site of exposure. We unexpectedly found that UVB-induced inflammation was not induced in gp91phox-depleted mice. To test whether gp91phox is directly involved in UVB-induced inflammation, neutrophil- and hyaluronic acid-depleted mice were also irradiated and examined for their response. Hyaluronic acid-depleted mice showed strongly inhibited UVB-induced inflammation, but the neutrophil-depleted mice did not exhibit any suppressed UVB-induced inflammation. To elucidate the pathway by which UVB irradiation induced inflammation, we examined the expression of nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) and caspase-1 in the mouse skin. An increase in the expression of NLRP3 and caspase-1 was seen following the UVB irradiation of C57BL mice; however, the UVB-irradiated gp91phox-knockout (gp91phox(-/-)) mice did not have this increase in expression. Furthermore, the plasma IL-1β level increased after the UVB irradiation in C57BL mice, but there was no change in the gp91phox(-/-) mice. These results clearly indicate that nicotinamide adenine dinucleotide phosphate oxidase is activated by gp91phox, which is expressed on the surface in response to the increased expression of hyaluronic acid induced by UVB irradiation, and as result, the generation of reactive oxygen species (ROS) increases. This ROS activate NLRP3, and NLRP3 leads to the production of caspase-1, which subsequently increases IL-1β, thereby finally inducing inflammation. It is thought that this system may play an important role in the damage and ageing of skin, and further studies are necessary to confirm these finding.
authors.affiliation: Department of Dermatology, Osaka City University Graduate School of Medicine, Osaka, Japan. hiramoto@msic.med.osaka-cu.ac.jp
authors.forename: Keiichi
authors.initials: K
authors.lastname: Hiramoto
authors.forename: Hiromi
authors.initials: H
authors.lastname: Kobayashi
authors.forename: Yurika
authors.initials: Y
authors.lastname: Yamate
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Ishii
authors.forename: Eisuke F
authors.initials: EF
authors.lastname: Sato
mesh_terms: D000208:Acute Disease; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D020170:Caspase 1 / Q000235:genetics / Q000378:metabolism; D061945:Caspase Inhibitors / Q000494:pharmacology; D003872:Dermatitis / Q000276:immunology* / Q000378:metabolism; D006820:Hyaluronic Acid / Q000378:metabolism*; D053583:Interleukin-1beta / Q000097:blood; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology* / Q000528:radiation effects*; D015595:Skin Aging / Q000276:immunology*; D013471:Sunburn / Q000276:immunology / Q000378:metabolism; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: D002352:Carrier Proteins; D061945:Caspase Inhibitors; D053583:Interleukin-1beta; D008562:Membrane Glycoproteins; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D017382:Reactive Oxygen Species; D006820:Hyaluronic Acid; C488842:Cybb protein, mouse; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; D020170:Caspase 1