Journal of Investigative Dermatology

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Poly(ADP-Ribose) Polymerase Mediates Inflammation in a Mouse Model of Contact Hypersensitivity

Peter Bai, Csaba Hegedu double acutes, Éva Szabó, László Gyüre, Edina Bakondi, Attila Brunyánszki, Szabolcs Gergely, Csaba Szabó and László Virág

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Supplementary Figure S1 (pdf 12K)

PJ34 inhibits TPA-induced irritant dermatitis. A. Mice (n=8) were treated with TPA for six hours and irritant dermatitis was quantified by measurement of ear thickness. TPA induced a moderate ear swelling as compared to oxazolone. PJ34 pretreatment significantly reduced swelling (n=8; *** p<0.001). B. Myeloperoxidase (MPO) activity of ear lysates also indicated granulocyte infiltration in the TPA group. MPO activity was efficiently reduced by PJ34 pretreatment. (n=5; *** p<0.001).

Supplementary Figure S2 (pdf 29K)

PARP regulates various steps of the inflammatory response in CHS. Activated leukocytes leave the bloodstream with the help of MMPs and secrete ROI/RNI as well as pro-inflammatory cytokines. The reactive species and the cytokines activate PARP in the nuclei of the resident and infiltrating cells, thus contributing to activation of NFkappaB, a master transcriptional regulator of inflammatory mediators. Of note, activation of NFkappaB can also be induced by oxidative stress. ROI/RNI also induce PARP activation in the endothelial cells and in skin resident cells leading to cell dysfunction. Endothelial cell dysfunction leads to increased vascular permeability resulting in the edema of the ears.

Supplementary Text (pdf 21K)

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