Extracellular Hsp72 A Doubleedged Sword For Host Defense

MONIKA FLESHNER*, JOHN D. JOHNSON AND JOSHUA FRIEDMAN

University of Colorado, Department of Integrative Physiology and the Center for Neuroscience, Boulder Colorado, USA

Abstract: Environmental or emotional challenge triggers a cascading series of physiological responses which are collectively termed the "stress response". The stress response can be assessed at the behavioral, neural, hormonal, immunological and single cell, levels and evolved to benefit an organism's chance of survival during times of acute challenge. The stress response has been studied for many years, however, its impact on specifically immune function has only recently been appreciated. Acute activation of the stress response has both inhibitory and stimulatory effects on immunity. The focus of this chapter is on a novel mechanism for the immunostimulatory effects of stress. Specifically, we propose that an endogenous, ubiquitous cellular stress protein, heat shock protein 72, when found in the extracellular environment may contribute to stress-induced potentiation of innate immunity. We develop the hypothesis that the release of extracellular heat shock protein 72 (eHsp72) is a normal feature of the acute stress response that can have either positive or negative consequences for host defense depending on several factors, including the nature of the eHsp72 (naked versus antigen-associated), and host health status (absence or presence of pre-existing inflammatory disease). Thus, stress-induced eHsp72 release may be a double-edged sword for host defense

Keywords: Danger signals, inflammation, stress, inflammatory bowel disease, sympathetic nervous system, a1adrenergic receptors

STRESS AND HEAT SHOCK PROTEINS Intracellular Hsp72

Heat-shock proteins (Hsp) are highly conserved cellular proteins that can be categorized into several families and play a role in a number of important cellular functions (Morimoto 1994). The first observations demonstrating the induction of intracellular heat shock proteins were reported in 1962 when Ritossa and colleagues noted that

'University of Colorado-Boulder, Department of Integrative Physiology, Campus Box 354, Boulder, CO 80309-0354, Phone: 303-492-1483, Fax: 303-492-6778, Email: [email protected]

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