Control of Islet Intercellular Adhesion Molecule-1 Expression by Interferon-α and Hypoxia

Abstract

The ability of interferon-alpha (IFN-alpha) to induce the adhesion molecules that characterize the islets of patients with type I diabetes has been investigated. We have found that all tested recombinant IFN-as will induce major histocompatibility complex (MHC) class I on arterial endothelial cells. Some but not all IFN-as will induce intercellular adhesion molecule-1 (ICAM-1). However, there is only a transient and modest increase in VCAM on arterial endothelial cells. IFN-alpha has very little effect on endothelial MHC class II expression but will induce these proteins on monocytes. Thus, there is a close concordance between the biological actions of IFN-alpha and the appearance of those adhesion molecules induced in the islets of patients with type I diabetes. IFN-alpha is also produced in normal human islets during short-term cultures, probably as a result of the ischemia present at the center of the islet. This induction of IFN-alpha by hypoxia may explain the previously reported spontaneous induction of ICAM-1 in human islets and may also be a contributing factor to the failure of islet grafts.

Nicotinamide decreases MHC class II but not MHC class I expression and increases intercellular adhesion molecule-1 structures in non-obese diabetic mouse pancreas

“…Moreover, NIC is not only capable of increasing the levels of IFN-and IL-4, but also of increasing the amount of IFN-, which efficiently induces MHC class I and ICAM-1 molecules (Chakrabarti et al 1996). Interestingly, islets from diabetic NOD animals in this study show high levels of IFN-(P<0·001 vs NON), though these levels were significantly lower with respect to those observed in NIC-treated NOD animals (P<0·001).…”

“…The expression of the proinflamatory Th1 cytokines IL-2 and TNF-predicts cell destruction in diabetic untreated NOD islets, whereas increased expression of a Th2 cytokine such as IL-4 is protective. Data demonstrate that NIC is able to significantly increase the levels of a protective Th2 cytokine and of IFN-, which in turn is known to be able to induce MHC class I and ICAM-1 but not MHC class II (Chakrabarti et al 1996). Moreover, NIC is not only able to increase IFNlevels but also IFN-, which efficiently are also able to induce MHC class I and ICAM-1 (Chakrabarti et al 1996).…”

“…Therefore, NIC seems to be able to significantly increase the levels of a protective Th2 cytokine, and also of IFN-, which is known to be able to induce MHC class I and ICAM-1 but not MHC class II molecules (Chakrabarti et al 1996). On the other hand, although IFN-is not itself considered to be a Th2 cytokine (Manetti et al 1995), it exerts several important anti-inflammatory actions, including an anti-diabetogenic role, suggested by the observation that poly I:C, an IFNinductor, protects NOD mice from diabetes (Rossini et al 1995).…”

“…Tissue non-specific cellular adhesion molecules (CAMs) have been interpreted as co-stimulatory molecules in the 'local' immune response (Yang et al 1996). It has also been shown that both interferon-(IFN-) and IFN-are able to induce MHC class I and ICAM-1, but not MHC class II, expression (Chakrabarti et al 1996). On the other hand, anti-ICAM-1 treatment has been shown to induce tolerance (Isobe et al 1992), and ICAM-1 expression in inflamed islets during disease progression up to 17 weeks of age does not appear to be modified (Yang et al 1996).…”

Persistent Infection of Human Pancreatic Islets by Coxsackievirus B Is Associated with Alpha Interferon Synthesis in β Cells

“…At 2 h p.i., islets were washed three times with phosphate-buffered saline (PBS) buffer and then resuspended in fresh growth medium and incubated at 37°C with 5% CO 2 . For virus titration assay, samples (islets plus supernatants) were collected on days 1,3,6,9,12,15,18,21,24,27,30,33,36, and 40 p.i., and then freeze-thawed three times, and after clarification, the supernatants were stored at Ϫ80°C until the titer for infectivity was determined with HEp-2 cells. Islet cultures mock infected with medium alone and the last washing solution recovered served as controls.…”