No abstract

HO-1 (haem oxygenase-1) is a stress-response enzyme involved in the catabolism of haem. In animal models, it plays a key protective role in vascular disease. HO-1 has anti-inflammatory effects in macrophages and is induced by a range of stimuli, including antioxidants, in various cell types. As dietary antioxidants are considered to be beneficial in vascular disease, their protective effects may occur through induction of HO-1. Emerging evidence suggests that a range of dietary and other naturally occurring antioxidants stimulate HO-1 expression in various cell types, although regulation by these compounds has not been investigated in detail. These studies suggest that HO-1 may be a target for dietary therapy in vascular disease.

Crohn’s disease is a chronic inflammatory condition most commonly affecting the ileum and colon. The aetiology of Crohn’s disease is complex and may include defects in peptidoglycan recognition, and/or failures in the establishment of intestinal tolerance. We have recently described a novel constitutive endogenous delivery system for the translocation of nanomineral-antigen-peptidoglycan (NAP) conjugates to antigen presenting cells (APCs) in intestinal lymphoid patches. In mice NAP conjugate delivery to APCs results in high surface expression of the immuno-modulatory molecule programmed death receptor ligand 1 (PD-L1). Here we report that NAP conjugate positive APCs in human ileal tissues from individuals with ulcerative colitis and intestinal carcinomas, also have high expression of PD-L1. However, NAP-conjugate positive APCs in intestinal tissue from patients with Crohn’s disease show selective failure in PD-L1 expression. Therefore, in Crohn’s disease intestinal antigen taken up by lymphoid patch APCs will be presented without PD-L1 induced tolerogenic signalling, perhaps initiating disease.

Leptin concentrations signal energy status from fetal life onward. As infancy progresses, leptin's power to discriminate both chronic and dynamic energy status increases, and this discrimination is achieved at much lower circulating peptide concentrations.