Expression of heat shock protein 32 (hemoxygenase-1) in the normal and inflamed human stomach and colon: an immunohistochemical study

Abstract

Heat shock protein 32 (Hsp32, hemoxygenase-1) is induced by reactive oxygen metabolites (ROM) and degrades heme leading to the formation of antioxidant bilirubin. Increased mucosal generation of ROM occurs in gastritis and inflammatory bowel disease. We aimed to assess mucosal expression of Hsp32 in normal stomach and colon and to test the hypothesis that disease-related differential expression occurs in inflamed tissue. Gastric body and antral mucosal biopsies were obtained from 33 patients comprising Helicobacter pylori-negative normal controls (n = 8), H pylori-negative gastritis patients (n = 11), and H pylori-positive gastritis patients (n = 14). Forty-seven archival colonic mucosal biopsies selected comprised normal histology (n = 10), active ulcerative colitis (UC) (n = 9), inactive UC (n = 8), active Crohn's disease (CD) (n = 8), inactive CD (n = 6), and other colitides (n = 6). Hsp32 expression in formalin-fixed sections was assessed by avidin-biotin peroxidase immunohistochemistry using a polyclonal rabbit anti-Hsp32 as the primary antibody. Immunohistochemical staining identified Hsp32 in all groups. Diffuse cytoplasmic staining was seen in gastric and colonic epithelial and lamina proprial inflammatory cells. Staining scores for Hsp32 were higher in antral H pylori-positive (P = 0.002) and H pylori-negative (P = 0.02) gastritis than in controls and in body H pylori-positive gastritis than in the other 2 groups (P < 0.01). Expression of Hsp32 was increased in active UC compared with inactive disease (P = 0.03) and normal controls (P = 0.02). In conclusion, Hsp32 is expressed constitutively in normal gastric and colonic mucosa, and differential expression occurs in these tissues when they are inflamed. Upregulation of Hsp32 may be an adaptive response to protect mucosa from oxidative injury in patients with gastritis and inflammatory bowel disease.

Molecular mechanism and functional consequences of lansoprazole-mediated heme oxygenase-1 induction

“…Our data support other work that has shown that Immunohistochemical studies have demonstrated that HO-1 is expressed constitutively in normal gastric and colonic mucosa and its upregulation occurs in these tissues during inflammation or the healing phase of gastric ulcers [28,29] . In the present study, significant HO-1 induction following treatment with lansoprazole in endothelial cells and macrophages, as well as antioxidant protection occurred at a concentration of 30 µmol/L.…”

Genetic Evidence for a Protective Role for Heat Shock Factor 1 and Heat Shock Protein 70 against Colitis

“…Because some HSPs have been reported to be overexpressed in the intestinal tissues of IBD patients (19,20,23) and in an animal model of IBD (21)(22)(23). HSF1 and HSPs are thought to be involved in the pathogenesis of IBD.…”

Heme Oxygenase-1 Is a Critical Regulator of Nitric Oxide Production in Enterohemorrhagic Escherichia coli-Infected Human Enterocytes

“…Thus, it is proposed that HO-1 serves as an adaptive mechanism to protect cells from oxidative stress (37). In this context, an increased expression of HO-1 has also been shown in pathophysiological states such as atherosclerosis (38), sepsis (39), Helicobacter pylori-positive and -negative gastritis, and ulcerative colitis (40); in these two last inflammatory diseases, HO-1 was immunodetected in superficial and cryptic epithelial cells. Additionally, the protective role of HO-1 has been demonstrated in experimental colitis in trinitrobenzene sulfonic acid and dextran sodium sulfate models (41,42), and in IL-10-deficient mice (43).…”