HSP60 is a Ubiquitous Player in the Physiological and Pathogenic Interactions between the Chaperoning and the Immune Systems

Abstract

HSP60 participates in many interactions between the system integrated by all chaperones and closely associated molecules (chaperoning system or CS) and the immune system (IS). These interactions occur constantly to maintain normal cell physiology but, occasionally, they are perturbed and become mediators of pathologic events that may lead to disease. This switch to pathology may be initiated by various factors, genetic or acquired, which cause qualitative and/or quantitative modifications of HSP60, or immune crossreactivity between the human and microbial chaperonin orthologs, or a break in the balance between the pro-and anti-inflammatory actions of the chaperonin. Thus, autoimmune and chronic inflammatory pathologies may occur. Likewise, a perturbation of the CS-IS interactions, e.g., those that take place during ageing, may favor carcinogenesis. HSP60 may be commandeered by tumor cells to assist its high-rate protein synthesis and, also, to be an emissary among the devices tumor cells utilize to avoid anti-tumor immune reactions. Here, we briefly discuss the canonical and non-canonical functions of HSP/chaperones; and HSP60 as a multifunctional molecule, its migration itinerary, and its possible roles during carcinogenesis and in certain chronic inflammatory and autoimmune diseases. We examine the potential of HSP60 as a biomarker useful for diagnosing and monitoring the progression of the various conditions in which it actively participates. Lastly, we discuss the use HSP60 as target for controlling its activity when it is an etiopathogenic factor, or as a therapeutic agent to correct its deficiency.

Immunomorphological Pattern of Molecular Chaperones in Normal and Pathological Thyroid Tissues and Circulating Exosomes: Potential Use in Clinics

“…These observations suggest that the chaperones may be secreted via extracellular vesicles, for instance. The cellular distribution of Hsps usually changes during the carcinogenic process [6,19,20,21]. Typically, they localize in the mitochondria (Hsp60) or in the cytoplasm of normal cells.…”

Hsp60 Post-translational Modifications: Functional and Pathological Consequences

“…Replication and transmission of mitochondrial DNA Kaufman et al, 2000Kaufman et al, , 2003 Protein folding Weiss et al, 2016 Pro-survival or pro-death functions Itoh et al, 2002;Chandra et al, 2007 Cytosol Pro-survival and/or pro-death functions Itoh et al, 2002;Chandra et al, 2007;Campanella et al, 2008;Chun et al, 2010;Caruso Bavisotto et al, 2017b;Zhou et al, 2018 Activation of the apoptotic cascade Gupta and Knowlton, 2005 Cell membrane Membrane transport, cell-cell signaling Belles et al, 1999;Dziewanowska et al, 2000;Pfister et al, 2005;Cappello et al, 2008;Merendino et al, 2010;Campanella et al, 2012;Caruso Bavisotto et al, 2017a Immune system alerting Habich and Burkart, 2007;Cappello et al, 2009;Marino Gammazza et al, 2017b Extracellular space…”

“…Hsp60 is a molecular chaperone that belongs to the chaperonins of Group I; it is named HSPD1 or Cpn60 in humans and is classically described as a mitochondrial resident that maintains protein homeostasis in the organelle. However, this chaperonin plays various other roles in health and disease, particularly as a pathogenic factor in a range of inherited and acquired chaperonopathies (Macario and Conway de Macario, 2005;Cappello et al, 2008Cappello et al, , 2013Cappello et al, , 2014Marino Gammazza et al, 2017b;Hoter et al, 2019;van Eden et al, 2019). For these reasons, interest in Hsp60 has been steadily increasing in recent years, especially because it holds promise for developing new diagnostic and therapeutic procedures pertinent to common and serious chaperonopathies such as various types of cancer, and inflammatory and autoimmune disorders as well as for a range of neurodegenerative diseases (Macario and Conway de Macario, 2005;Cappello et al, 2008;Bross et al, 2012;Cappello et al, 2013Cappello et al, , 2014Marino Gammazza et al, 2016Campanella et al, 2018;Meng et al, 2018;Hoter et al, 2019;van Eden et al, 2019).…”

“…Hsp60 occurs not only inside mitochondria but also in other intracellular locations, for example the cytosol, and extracellularly, and its functions vary accordingly, depending on the interactors that surround it at the various locations. For example, inside mitochondria Hsp60 assists the folding and trafficking of other proteins, but in the cytosol it can favor apoptosis or the contrary, for example in some cancer cells, and can thus be anti-or pro-cancer, respectively (Campanella et al, 2014;Marino Gammazza et al, 2017b).…”

Extracellular Heat Shock Proteins as a Natural Protector of Cells and Organisms: A Review of Recent Studies

“…As Gammazza et al discuss [130], the immune system evolved later with respect to the chaperoning system, and the chaperoning system and the immune system probably complemented each other and interacted to ensure organismal homeostasis and survival. As we have considered above, in the immune system, HSPs appear to generally exhibit antiinflammatory and immunosuppressive effects, but modulate or enhance inflammatory signals and assist antigen-specific immune responses.…”