Differential expression of multiple kallikreins in a viral model of multiple sclerosis points to unique roles in the innate and adaptive immune response

Michael Panos, George P. Christophi, Moses Rodriguez, Isobel A Scarisbrick

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Recent studies provide a functional link between kallikrein 6 (Klk6) and the development and progression of disease in patients with multiple sclerosis (MS) and in its murine models. To evaluate the involvement of additional kallikrein family members, we compared Klk6 expression with four other kallikreins (Klk1, Klk7, Klk8, and Klk10) in the brain and spinal cord of mice infected with Theiler's murine encephalomyelitis virus, an experimental model of progressive MS. The robust upregulation of Klk6 and Klk8 in the brain during the acute phase of viral encephalitis and in the spinal cord during disease development and progression points to their participation in inflammation, demyelination, and progressive axon degeneration. More limited changes in Klk1, Klk7, and Klk10 were also observed. In addition, Klk1, Klk6, and Klk10 were dynamically regulated in T cells in vitro as a recall response to viral antigen and in activated monocytes, pointing to their activities in the development of adaptive and innate immune function. Together, these results point to overlapping and unique roles for multiple kallikreins in the development and progression of virusmediated central nervous system inflammatory demyelinating disease, including activities in the development of the adaptive and innate immune response, in demyelination, and in progressive axon degeneration.

Original languageEnglish (US)
Pages (from-to)1063-1073
Number of pages11
JournalBiological Chemistry
Volume395
Issue number9
DOIs
StatePublished - Sep 1 2014

Fingerprint

Kallikreins
Adaptive Immunity
Innate Immunity
Multiple Sclerosis
Demyelinating Diseases
Axons
Disease Progression
Brain
Theilovirus
Viral Encephalitis
T-cells
Viral Antigens
Spinal Cord Diseases
Neurology
Viruses
Monocytes
Spinal Cord
Theoretical Models
Up-Regulation
Central Nervous System

Keywords

  • Axon injury
  • Demyelination
  • Inflammation
  • Multiple sclerosis
  • Serine protease
  • Theiler's murine encephalomyelitis virus

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Molecular Biology

Cite this

Differential expression of multiple kallikreins in a viral model of multiple sclerosis points to unique roles in the innate and adaptive immune response. / Panos, Michael; Christophi, George P.; Rodriguez, Moses; Scarisbrick, Isobel A.

In: Biological Chemistry, Vol. 395, No. 9, 01.09.2014, p. 1063-1073.

Research output: Contribution to journalArticle

@article{31b4a442debe4a9e9b91da55b127ac31,
title = "Differential expression of multiple kallikreins in a viral model of multiple sclerosis points to unique roles in the innate and adaptive immune response",
abstract = "Recent studies provide a functional link between kallikrein 6 (Klk6) and the development and progression of disease in patients with multiple sclerosis (MS) and in its murine models. To evaluate the involvement of additional kallikrein family members, we compared Klk6 expression with four other kallikreins (Klk1, Klk7, Klk8, and Klk10) in the brain and spinal cord of mice infected with Theiler's murine encephalomyelitis virus, an experimental model of progressive MS. The robust upregulation of Klk6 and Klk8 in the brain during the acute phase of viral encephalitis and in the spinal cord during disease development and progression points to their participation in inflammation, demyelination, and progressive axon degeneration. More limited changes in Klk1, Klk7, and Klk10 were also observed. In addition, Klk1, Klk6, and Klk10 were dynamically regulated in T cells in vitro as a recall response to viral antigen and in activated monocytes, pointing to their activities in the development of adaptive and innate immune function. Together, these results point to overlapping and unique roles for multiple kallikreins in the development and progression of virusmediated central nervous system inflammatory demyelinating disease, including activities in the development of the adaptive and innate immune response, in demyelination, and in progressive axon degeneration.",
keywords = "Axon injury, Demyelination, Inflammation, Multiple sclerosis, Serine protease, Theiler's murine encephalomyelitis virus",
author = "Michael Panos and Christophi, {George P.} and Moses Rodriguez and Scarisbrick, {Isobel A}",
year = "2014",
month = "9",
day = "1",
doi = "10.1515/hsz-2014-0141",
language = "English (US)",
volume = "395",
pages = "1063--1073",
journal = "Biological Chemistry",
issn = "1431-6730",
publisher = "Walter de Gruyter GmbH & Co. KG",
number = "9",

}

TY - JOUR

T1 - Differential expression of multiple kallikreins in a viral model of multiple sclerosis points to unique roles in the innate and adaptive immune response

AU - Panos, Michael

AU - Christophi, George P.

AU - Rodriguez, Moses

AU - Scarisbrick, Isobel A

PY - 2014/9/1

Y1 - 2014/9/1

N2 - Recent studies provide a functional link between kallikrein 6 (Klk6) and the development and progression of disease in patients with multiple sclerosis (MS) and in its murine models. To evaluate the involvement of additional kallikrein family members, we compared Klk6 expression with four other kallikreins (Klk1, Klk7, Klk8, and Klk10) in the brain and spinal cord of mice infected with Theiler's murine encephalomyelitis virus, an experimental model of progressive MS. The robust upregulation of Klk6 and Klk8 in the brain during the acute phase of viral encephalitis and in the spinal cord during disease development and progression points to their participation in inflammation, demyelination, and progressive axon degeneration. More limited changes in Klk1, Klk7, and Klk10 were also observed. In addition, Klk1, Klk6, and Klk10 were dynamically regulated in T cells in vitro as a recall response to viral antigen and in activated monocytes, pointing to their activities in the development of adaptive and innate immune function. Together, these results point to overlapping and unique roles for multiple kallikreins in the development and progression of virusmediated central nervous system inflammatory demyelinating disease, including activities in the development of the adaptive and innate immune response, in demyelination, and in progressive axon degeneration.

AB - Recent studies provide a functional link between kallikrein 6 (Klk6) and the development and progression of disease in patients with multiple sclerosis (MS) and in its murine models. To evaluate the involvement of additional kallikrein family members, we compared Klk6 expression with four other kallikreins (Klk1, Klk7, Klk8, and Klk10) in the brain and spinal cord of mice infected with Theiler's murine encephalomyelitis virus, an experimental model of progressive MS. The robust upregulation of Klk6 and Klk8 in the brain during the acute phase of viral encephalitis and in the spinal cord during disease development and progression points to their participation in inflammation, demyelination, and progressive axon degeneration. More limited changes in Klk1, Klk7, and Klk10 were also observed. In addition, Klk1, Klk6, and Klk10 were dynamically regulated in T cells in vitro as a recall response to viral antigen and in activated monocytes, pointing to their activities in the development of adaptive and innate immune function. Together, these results point to overlapping and unique roles for multiple kallikreins in the development and progression of virusmediated central nervous system inflammatory demyelinating disease, including activities in the development of the adaptive and innate immune response, in demyelination, and in progressive axon degeneration.

KW - Axon injury

KW - Demyelination

KW - Inflammation

KW - Multiple sclerosis

KW - Serine protease

KW - Theiler's murine encephalomyelitis virus

UR - http://www.scopus.com/inward/record.url?scp=84926343704&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84926343704&partnerID=8YFLogxK

U2 - 10.1515/hsz-2014-0141

DO - 10.1515/hsz-2014-0141

M3 - Article

C2 - 25153387

AN - SCOPUS:84926343704

VL - 395

SP - 1063

EP - 1073

JO - Biological Chemistry

JF - Biological Chemistry

SN - 1431-6730

IS - 9

ER -