Soluble CD40 ligand disrupts the blood-brain barrier and exacerbates inflammation in experimental autoimmune encephalomyelitis

Hiroki Masuda; Masahiro Mori; Kenta Umehara; Tomomi Furihata; Tomohiko Uchida; Akiyuki Uzawa; Satoshi Kuwabara

doi:10.1016/j.jneuroim.2018.01.001

Soluble CD40 ligand disrupts the blood-brain barrier and exacerbates inflammation in experimental autoimmune encephalomyelitis

J Neuroimmunol. 2018 Mar 15:316:117-120. doi: 10.1016/j.jneuroim.2018.01.001. Epub 2018 Jan 3.

Authors

Hiroki Masuda¹, Masahiro Mori², Kenta Umehara³, Tomomi Furihata⁴, Tomohiko Uchida⁵, Akiyuki Uzawa⁶, Satoshi Kuwabara⁷

Affiliations

¹ Department of Neurology, Graduate School of Medicine, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba 260-8670, Japan. Electronic address: hiroki_masuda@msn.com.
² Department of Neurology, Graduate School of Medicine, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba 260-8670, Japan. Electronic address: morim@faculty.chiba-u.jp.
³ Laboratory of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba 260-8670, Japan. Electronic address: dive_k_um_sea@hotmail.com.
⁴ Laboratory of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba 260-8670, Japan; Department of Pharmacology, Graduate School of Medicine, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba 260-8670, Japan. Electronic address: tomomif@faculty.chiba-u.jp.
⁵ Department of Neurology, Graduate School of Medicine, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba 260-8670, Japan. Electronic address: n9n13@hotmail.com.
⁶ Department of Neurology, Graduate School of Medicine, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba 260-8670, Japan. Electronic address: auzawa@chiba-u.jp.
⁷ Department of Neurology, Graduate School of Medicine, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba 260-8670, Japan. Electronic address: kuwabara-s@faculty.chiba-u.jp.

PMID: 29329699
DOI: 10.1016/j.jneuroim.2018.01.001

Abstract

Serum soluble CD40 ligand (sCD40L) has been reported to positively correlate with the albumin quotient, a marker of blood-brain barrier (BBB) breakdown, in patients with multiple sclerosis (MS). To clarify the mechanisms of sCD40L in MS pathophysiology, sCD40L was administered to experimental autoimmune encephalomyelitis (EAE) mice and a human brain microvascular endothelial cell (HBMEC)-based BBB model. The high-dose sCD40L group showed a worse EAE score than the low-dose and control groups. BBB permeability was increased by administering sCD40L in a HBMEC-based BBB model. Thus, sCD40L induces more severe inflammation in the central nervous system by disrupting the BBB.

Keywords: Blood–brain barrier; Experimental autoimmune encephalomyelitis; Multiple sclerosis; Soluble CD40 ligand.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Blood-Brain Barrier / pathology*
CD40 Antigens*
Capillary Permeability*
Encephalomyelitis, Autoimmune, Experimental / pathology*
Female
Inflammation / pathology*
Mice
Mice, Inbred C57BL

Substances

CD40 Antigens