Changes in Immunohistochemical Levels and Subcellular Localization After Therapy and Correlation and Colocalization With CD68 Suggest a Pathogenetic Role of Hsp60 in Ulcerative Colitis

Abstract

Abstract:In an earlier work, the role of heat shock protein (Hsp60) in the pathogenesis of ulcerative colitis (UC) was suggested by its significant increase in the pathological mucosa parallel with an increase in inflammatory cells. More data in this direction are reported in this work. We analyzed by immunohistochemistry biopsies of colon tissue from 2 groups of patients with UC and treated with either 5-aminosalicylic acid (5-ASA) alone or in combination with a probiotic. We looked for inflammatory markers and Hsp60. Both the treatments were effective in reducing symptoms but the group treated with both 5-ASA and probiotics showed better clinical results. Amelioration of symptoms was associated with reduction of both inflammation and Hsp60, a reduction that was most marked in the group treated with 5-ASA and probiotics. The levels of Hsp60 positively correlated with those of CD68-positive cells, and double immunofluorescence showed a high index of colocalization of the chaperonin and CD68 in lamina propria. Immunoelectron microscopy showed that Hsp60Fclassically a mitochondrial proteinFwas abundantly also present in cytosol in biopsies taken at the time of diagnosis, but not after the treatment. Our data suggest that Hsp60 is an active player in pathogenesis of UC and it can be hypothesized that the chaperonin is responsible, at least in part, for initiation and maintenance of disease.

Hsp10, Hsp70, and Hsp90 immunohistochemical levels change in ulcerative colitis after therapy

“…13 Disease activity was assessed using the Mayo Score system from 0 to 12. 14 Mildly to moderately disease activity was defined by a score of 4 to 10.…”

Pharmacogenetics in inflammatory bowel disease: understanding treatment response and personalizing therapeutic strategies

“…They also demonstrated that Hsp90 levels are elevated in colonic mucosa from UC patients, both in epithelium and lamina propria 19. Treatment with 5-ASA plus probiotics reduced the Hsp90 levels in the lamina propria, while 5-ASA alone did not have any effect and a linear correlation was also reported between Hsp90 and CD4 levels in lamina propria in UC patients at both diagnosis and 6 months after 5-ASA only therapy 20…”

Chaperonotherapy for Alzheimer’s Disease: Focusing on HSP60

“…HSP60 influences the pro-inflammatory capacity of adipocytes binding an adipocyte receptor, contributing to obesity-associated inflammatory disease leading to diabetes [89]. HSP60 has been also involved in the pathogenesis of chronic inflammatory diseases such as Crohn's disease [90], ulcerative colitis [90,91], chronic obstructive pulmonary disease [92], and atherosclerosis [93].…”