019 KLK6-PAR1 signaling drives psoriasiform manifestations in skin and bone

Expression of Par1 in Squamous Cell Skin

PAR1 is proposed to be involved in variety of invasive and metastatic cancers. Its expression correlates with the degree of invasiveness in some tissues and cancer cell lines. The aim of this study was to analyze the expression of PAR1 in human squamous cell carcinomas with different grade of differentiation. Immunohistochemical analysis in human SCCs and healthy skin was performed to evaluate ...

Psoriasiform skin eruption associated with sorafenib therapy.

IL-12 protects from psoriasiform skin inflammation

Neutralization of the common p40-subunit of IL-12/23 in psoriasis patients has led to a breakthrough in the management of moderate to severe disease. Aside from neutralizing IL-23, which is thought to be responsible for the curative effect, anti-p40 therapy also interferes with IL-12 signalling and type 1 immunity. Here we dissect the individual contribution of these two cytokines to the format...

Kallikrein 6 signals through PAR1 and PAR2 to promote neuron injury and exacerbate glutamate neurotoxicity.

CNS trauma generates a proteolytic imbalance contributing to secondary injury, including axonopathy and neuron degeneration. Kallikrein 6 (Klk6) is a serine protease implicated in neurodegeneration, and here we investigate the role of protease-activated receptors 1 (PAR1) and PAR2 in mediating these effects. First, we demonstrate Klk6 and the prototypical activator of PAR1, thrombin, as well as...

IL-1R1 signaling facilitates Munro’s microabscess formation in psoriasiform imiquimod-induced skin inflammation

Munro's microabscesses contain polymorphonuclear leukocytes and form specifically in the epidermis of psoriasis patients. The mechanism whereby the neutrophils are recruited into the epidermis is poorly understood. Using a combination of human and mouse primary keratinocyte cell cultures and the imiquimod-induced psoriasis-like mouse model of skin inflammation, we explored the role of IL-1 sign...