title: Kallikrein-related peptidase 6 exacerbates disease in an autoimmune model of multiple sclerosis.
abstract: Kallikrein-related peptidase 6 (Klk6) is elevated in the serum of multiple sclerosis (MS) patients and is hypothesized to participate in inflammatory and neuropathogenic aspects of the disease. To test this hypothesis, we investigated the impact of systemic administration of recombinant Klk6 on the development and progression of MOG35-55-induced experimental autoimmune encephalomyelitis (EAE). First, we determined that Klk6 expression is elevated in the spinal cord of mice with EAE at the peak of clinical disease and in immune cells upon priming with the disease-initiating peptide in vitro. Systemic administration of recombinant Klk6 to mice during the priming phase of disease resulted in an exacerbation of clinical symptoms, including earlier onset of disease and higher levels of spinal cord inflammation and pathology. Treatment of MOG35-55-primed immune cells with Klk6 in culture enhanced expression of pro-inflammatory cytokines, interferon-γ, tumor necrosis factor, and interleukin-17, while reducing anti-inflammatory cytokines interleukin-4 and interleukin-5. Together these findings provide evidence that elevations in systemic Klk6 can bias the immune system towards pro-inflammatory responses capable of exacerbating the development of neuroinflammation and paralytic neurological deficits. We suggest that Klk6 represents an important target for conditions in which pro-inflammatory responses play a critical role in disease development, including MS.
authors.forename: Hyesook
authors.initials: H
authors.lastname: Yoon
authors.forename: Isobel A
authors.initials: IA
authors.lastname: Scarisbrick
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D007610:Kallikreins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000201:enzymology* / Q000276:immunology / Q000378:metabolism; D013116:Spinal Cord / Q000201:enzymology; D013154:Spleen / Q000276:immunology
chemical_list: D007610:Kallikreins; C491223:Prss18 protein, mouse