ABSTRACT
Indolemine 2, 3-dioxygenase [IDO] is a cytosolic monomeric hemoprotein enzyme that catalyses tryptophan, the least available essential amino acid in the human body, to N-formylkynurenine, which in turn rapidly degrades to give kynurenine. IDO is expressed in different tissues, especially and prominently in some subsets of antigen presenting cells [APCs] of lymphoid organs and also in the placenta of human and other mammals. Expression of IDO by certain dendritic cells, monocytes and macrophages has a regulatory effect on T cells probably by providing a tryptophan-deficient microenvironment and/or accumulation of toxic metabolites of tryptophan. This immunomodulatory function of IDO plays an essential role in different physiological and pathological states. IDO was shown to prevent rejection of the fetus during pregnancy, possibly by inhibiting alloreactive T cells. Moreover, IDO expression in APCs was suggested to control autoreactive immune responses. In this review we discuss the molecular and biological characteristics of IDO and its function in immune system as well as the potential application of this enzyme in improving the outcome of allogeneic transplantation as a local immunosuppressive factor
ABSTRACT
This study was conducted to examine if allergic contact dermatitis [ACD] alters the expression ofMMPs in human dermal fibroblasts. Fibroblasts are the primary source for MMP and matrix production in skin. MMPs are known to involve in a number of physiological and pathological processes. Some published data indicated a gelatinaselike activity in acute and chronic phases of allergic contact dermatitis. However, no exact source of gelatinase activity was demonstrated. Moreover, little is known about the role of MMPs in immune responses. To study and predict the pathophysiological effects of [MMP-2] in allergic contact dermatitic [ACD] patients, we established an in vitro tissue culture survey based on fibroblast explanted from ACD wounds and normal tissues respectively. We also employed a precise proliferation assay [i.e. MTT; 3-[4,5-dimethylthiazol-2-yl]-2,5- diphenyltetrazolium bromide] to analyze and compare three ACD vs. three normal cell strains Parallel to MTT assay, we assessed the activity as well as the kinetics of gelatinase [MMP-2] in conditioned media using a zymogeraphy analysis. There was a significant difference in proliferation capacity between mean ACD fibroblast strains vs. mean normal cells, particularly in days 6 to 8 post explantation, 492.5 +/- 6.6 vs. 361.75 +/- 8.25 respectively. Zymoanalyses indicated significant differences betweenACD cells and normal fibroblasts both in time-course and MMP-2 activity per cell fashions, 163.7 +/- 16.21 for meanACD fibroblasts vs. 130 +/- 9.09 for normal cells respectively. These data suggest that fibroblasts overproliferated in the process ofACD. Moreover, simultaneous overexpression of MMPs observed inACD fibroblasts vs. normal strains, is indicative of altered fibroblast functionality in the process of allergic contact dermatitis. The activity per cell analysis showed that MMP-2 expression in ACD fibroblasts is independent of cell number, suggesting that either intra- or inter-cellular control signals are also altered and that ACD fibroblasts exhibit hyper-responsiveness to mitogenic or fibrogenic stimulants. Altogether, these data address the chronocity and non-healing tendency of ACD wounds. However, more studies are required to examine possible MMPs inhibition and differential expression of mytogenic, fibrogenic and antifibrogenic cytokines in ACD wound beds. In particular, MMP-2 is postulated to be an aim for further gene therapy protocols