Sera from CIDP patients disrupt blood-nerve barrier via activation of rho-kinase pathway

Abstract

Objective: In our recent in vitro study, sera from chronic inflammatory demyelinating polyneuropathy (CIDP) patients were shown to possess effects to disrupt blood-nerve barrier (BNB). We studied the molecular background of BNB damage in CIDP using patients’ sera and cultured microvascular endothelial cells derived from human peripheral nerve (PnMECs). Methods: We have obtained patient and Institutional Review Board (IRB) approval, as necessary. We evaluated the effects of sera obtained from patients with CIDP on the expression levels of tight junction proteins, intercellular cell adhesion molecule-1 (ICAM-1), actin stress fiber formation and transendothelial electrical resistance (TEER) value in the PnMECs. We then investigated the influence of the CIDP sera on PnMECs in the presence of specific rho-kinase inhibitor (Y-27632) in order to determine whether rho-kinase pathway is involved in BNB alterations induced by patients’ sera. Results: The sera obtained from the patients with CIDP significantly decreased the amount of claudin-5 and ZO-1 protein levels and TEER values in the PnMECs as compared with normal controls. CIDP sera also increased ICAM-1 protein amount and actin stress fiber formation. Treatment with Y-27632 attenuated reduction of TEER values and claudin-5 expression levels induced by CIDP sera. Y-27632 treatment also prevented the increase of ICAM-1protein amount and excessive actin stress fiber formation. Conclusion: Humoral factors in the sera of CIDP patients may disrupt BNB via activation of rho-kinase pathway.