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Its precise role during inflammation and the underlying mechanisms is still unclear. Our study establishes that PAR\u20102 plays a direct proinflammatory role during cutaneous inflammation in mice and humans in vivo. In a model of experimentally induced allergic (ACD) and toxic (ICD) contact dermatitis (CD) we show that ear swelling responses, plasma extravasation, and leucocyte adherence were significantly attenuated in PAR\u20102 null mutant (PAR\u20102\n                    <jats:sup>\u22127\u2212<\/jats:sup>\n                    ) mice compared with wild\u2010type (PAR\u20102\n                    <jats:sup>+\/+<\/jats:sup>\n                    ) mice, especially at early stages. The proinflammatory effects by PAR\u20102 activation were significantly diminished using nitric oxide\u2010synthase inhibitors, while NF\u2010kappaB and neuropeptides appear to play a minor role in these mechanisms. PAR\u20102\u2010mediated up\u2010regulation of E\u2010selectin and cell adhesion molecule ICAM\u20101;enhanced plasma extravasation was observed in humans and mice and of interleukin\u20106 in mice in vivo. Thus, PAR\u20102 may be a beneficial therapeutic target for the treatment of inflammatory skin diseases.\u2014 Seeliger, S., Derian, C. K., Vergnolle, N., Bunnett, N. W., Nawroth, R., Schmelz, M., von der Weid, P.\u2010Y., Buddenkotte, J., Sunderko\u00a8tter, C., Metze, D., Andrade\u2010 Gordon, P., Harms, E., Vestweber, D., Luger, T. A., Steinhoff, M. 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