Up-regulation of inducible heat shock protein-70 expression in multiple sclerosis patients

Abstract

Inducible heat shock protein (HSP)70 (HSP70-1A and HSP70-1B proteins) is a chaperone responsible for assisting proper protein folding. Following stress conditions, HSP70 is highly up-regulated to mediate cytoprotective functions. In addition, HSP70 is able to trigger innate and adaptive immune responses that promote the immune recognition of antigens and to act as a cytokine when it is released. The data in the literature are controversial with regard to expression studies in peripheral blood mononuclear cells (PBMCs). In the present study, we aimed to examine if alterations of HSP70-1A/B expression are involved in the autoimmune pathogenesis of multiple sclerosis (MS). We determined both mRNA and protein expression in PBMCs of MS patients and healthy donors (HDs). We found a baseline increased expression of the HSPA1A gene in PBMCs from MS patients compared with HDs. Gene expression findings were associated with an increased protein expression of HSP70-1A/B in T lymphocytes (CD4+ and CD8+) and monocytes from MS patients under basal conditions that may reflect the immunological activation occurring in MS patients. We also provided evidence that heat shock (HS) stimulus induced HSP70-1A/B protein expression in HDs and MS patients, and that HS-induced HSP70-1A/B protein expression in monocytes correlated with the number of T2 lesions at baseline in MS patients. However, after lipopolysaccharide inflammatory stimulus, monocytes from MS patients failed to induce HSP70-1A/B protein expression. Our data hint at altered immune responses in MS and may indicate either a state of chronic stress or increased vulnerability to physiological immune responses in MS patients.

• Autoimmunity
• heat shock protein
• HSPA1A
• immune regulation
• multiple sclerosis

Acknowledgements

We are grateful to the patients and healthy donors who agreed to participate in this study and to our nurses, Mrs. R. Horno and M. J. Vicente, for their efficient clinical/basic coordination in the provision of patient material. We thank the “Red Española de Esclerosis Múltiple (REEM)” (RD12/0032) – sponsored by the Fondo de Investigación Sanitaria (FIS), Ministry of Economy and Competition Spain – and the “Ajuts per donar Suport als Grups de Recerca de Catalunya (2009 SGR 0793)”, sponsored by the “Agència de Gestió d’Ajuts Universitaris i de Recerca” (AGAUR), Generalitat de Catalunya, Spain. CE is partially supported by the “Miguel Servet” program (CP07/00146) from the FIS, Ministry of Economy and Competition, Spain.