Hsp60 as a Novel Target in IBD Management: A Prospect

Abstract

Inflammatory bowel disease (IBD) encompasses various pathological conditions similar but distinct that share a multifactorial etiology, including involvement of the intestinal barrier function, the immune system, and intestinal microorganisms. Hsp60 is a chaperonin component of the chaperoning system, present in all cells and tissues, including the intestine. It plays important roles in cell physiology outside and inside mitochondria, its canonical place of residence. However, Hsp60 can also be pathogenic in many conditions, the Hsp60 chaperonopathies, possibly including IBD. The various clinico-pathological types of IBD have a complicated mix of causative factors, among which Hsp60 can be considered a putatively important driver of events and could play an etiopathogenic role. This possibility is discussed in this review. We also indicate that Hsp60 can be a biomarker useful in disease diagnosing and monitoring and, if found active in pathogenesis, should become a target for developing new therapies. The latter are particularly needed to alleviate patient suffering and to prevent complications, including colon cancer.

Probiotics Can Cure Oral Aphthous-Like Ulcers in Inflammatory Bowel Disease Patients: A Review of the Literature and a Working Hypothesis

“…It is thought that they may be related to: Alteration of Treg/Th17 due to dysregulated TLRs on antigen-presenting cells [27];Resistance to colonization, i.e., ability of the gut microbiota to limit the proliferation of external pathogens. It has been observed that in patients with autoimmune disorders (e.g., systemic lupus erythematosus), resistance to colonization was lower than in healthy controls;Superantigens, derived from bacteria and viruses that have the ability to activate immune cells by simultaneously binding to the major proteins of the class II histocompatibility complex (MHC II) present in the antigen-presenting cells and to specific receptors present in activated T cells [32];Alteration of host antigens and overproduction of autoantigens; in particular, microbiota induces modification of host proteins and creation of neoantigens [27,33];Mucosal responses to microbiota, i.e., inflammatory cytokines that activate nearby autoreactive cells [30];Molecular mimicry, i.e., cross-reactive antibody that recognizes shared epitopes of microbial and host tissue proteins, and activation of autoreactive T and B cells [29,34,35]. …”

“…Mucosal responses to microbiota, i.e., inflammatory cytokines that activate nearby autoreactive cells [30];…”

“…However, in living subjects, the mucosal layer is characterized by the presence of a mix of symbiotic and pathogenic bacteria embedded in the mucus, produced by the epithelial cells. In this mucous matrix, apart from bacteria, are present a number of soluble substances and nanovesicles (i.e., exosomes, microvesicles and outer membrane vesicles), produced by both human cells and bacteria, that actively participate in the regulation of the homeostasis of the intestinal mucosa and, consequently, through lymphatic and hematic circulation, of virtually all of the organs [28,29,30]. Therefore, as already proposed [22], this mucus-microbiotic layer can be considered the real innermost layer of the intestinal wall.…”

Elongated Flexuous Plant Virus-Derived Nanoparticles Functionalized for Autoantibody Detection

“…We have explored the deployment of Heat Shock Protein 60 (Hsp60) as a possible autoantigen in IBD, due to the implication of Hsp60 in inflammatory processes [22,23,24,25,26,27,28,29,30,31], including IBD [32,33,34,35]. Heat shock proteins are a broad family of molecular chaperons capable of reacting to cellular stress, especially in thermal changes.…”

“…Hsp60, despite being a protein whose main function occurs in the mitochondria, is able to act in the cytoplasm modulating the immune response associated with inflammation. Both the complete protein and the peptides derived therefrom can act as natural regulators of the inflammatory reaction together with other cytokines, chemokines, and autoantibodies, regulating the immune system [30,32,36,37,38,39]. The activity of Hsp60 has been associated with various autoimmune and inflammatory pathologies, such as atherosclerosis, diabetes, rheumatoid arthritis, or multiple sclerosis [23,25,29,40,41,42].…”