Hsp60 and Hsp10 increase in colon mucosa of Crohn’s disease and ulcerative colitis

Abstract

The purpose of this work was to determine in colon mucosa of Crohn's disease (CD) and ulcerative colitis (UC) in relapse: a) the levels of the chaperonins Hsp60 and Hsp10; b) the quantity of inflammatory cells; and c) if the levels of chaperonins parallel those of inflammation cells. Twenty cases of CD and UC and twenty normal controls (NC) were studied using immunohistochemistry, Western blotting and immunofluorescence. Immunohistochemically, Hsp60 and Hsp10 were increased in both inflammatory bowel diseases (IBD) compared to NC. These results were confirmed by Western blotting. Hsp60 and Hsp10 occurred in the cytoplasm of epithelial cells in CD and UC but not in NC. Hsp60 and Hsp10 co-localised to epithelial cells of mucosal glands but not always in connective tissue cells of lamina propria, where only Hsp60 or, less often, Hsp10 was found. Cells typical of inflammation were significantly more abundant in CD and UC than in NC. Since chaperonins are key factors in the activation of the immune system leading to inflammation, we propose that they play a central role in the pathogenesis of the two diseases, which, consequently, ought to be studied as chaperonopathies.

Hsp60 chaperonopathies and chaperonotherapy: targets and agents

“…The actions of Hsp60 could lead to the modification of those proteins, and in this manner it could have a role in many diseases, including carcinogenesis. Heart Heart failure; Coronary vascular disease [137][138][139][140] Kidney Glomerulonephritis [141] Large bowel Inflammatory bowel diseases [19,142,143] Lung Chonic obstructive pulmonary disease [20] Oral cavity Periodontitis [144,145] Pancreas Type 1 diabetes [146][147][148][149][150][151] Skin Scleroderma, pemphigoid; Psoriasis; Dermatomyositis [152,153] Synovial joints Rheumatoid arthritis; Juvenile idiopathic arthritis [154][155][156][157] Vessels Vasculitis; Atherosclerosis [158][159][160][161][162][163][164][165][166][167] Adapted from [2]. Hsp60 seems to contribute to tumor cell survival, but this is controversial.…”

Gut microbiota imbalance and chaperoning system malfunction are central to ulcerative colitis pathogenesis and can be counteracted with specifically designed probiotics: a working hypothesis

“…The facts that HSP60 levels in the mucosa of UC patients are increased, compared to the mucosa of healthy individuals and significantly correlate with severity of clinical manifestations support the notion that the chaperonin is involved in UC pathogenesis [9,49,50]. Furthermore, UC treatment showed that the more clinically efficacious is the treatment, the more marked is the decrease in HSP60 (as well as in other inflammatory markers) levels in the colon mucosa, to the point that in complete remission the chaperonin levels are those typical of the normal intestine [50].…”

“…For instance, HSP60 is specifically induced by increments of colonic motility, 5-hydroxytryptamine administration, thyrotropin-releasing hormone, and waterimmersion stress [89]. In addition, we and others collected data by various techniques suggesting that HSPs might be involved in UC pathogenesis [9,61] and in colorectal carcinogenesis as well [90][91][92][93]. We recently reported that probiotics in combination with standard antibiotic therapy significantly reduced the levels of HSP10, HSP60, HSP70, and HSP90 in the mucosa of UC patients [49,50].…”

“…Our group in the past proposed, as a working hypothesis, that some chronic inflammatory and autoimmune diseases could be considered for the purposes of investigation and clinicopathological approach as models of chaperonopathies by mistake. Among the latter, we may cite chronic obstructive pulmonary disease [8], IBD [9], myasthenia gravis [10], and other autoimmune diseases such as those listed in Table 3 [11]. The interplay between the chaperoning and the immune systems of any given organism can in principle occur at least in three ways, involving mechanisms pertaining to innate or adaptive immunity and cell signaling in a hormonal fashion [12][13][14].…”

“…HSPs have been found increased in UC, both in tissue and serum [9,[61][62][63]. Pathological effects of HSPs in UC could be due to one or more of the following mechanisms ( Fig.…”