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The matrix metalloproteinase collagenase is expressed by resident tissue cells only when needed for biological remodeling. Exogenous addition of inflammatory and growth-promoting cytokines stimulates collagenase expression in early passage fibroblast cultures. In addition, the signal for collagenase expression in response to phorbol-12 myristate-13 acetate (PMA) or to agents which alter cell shape in early passage fibroblast cultures is routed extracellularly to an autocrine cytokine intermediate, IL-1 alpha. Importantly, fibroblasts, when freshly isolated from the tissue, are not competent for IL-1 alpha gene expression and, therefore, cannot produce collagenase in response to shape change agents. However, they do make a small amount of collagenase in response to PMA via an IL-1-independent pathway that has not been further characterized. In this paper, we investigate the role of a second autocrine, serum amyloid A3 (SAA3), in IL-1-dependent and -independent collagenase gene expression. We demonstrate that SAA3 is required for effective stimulation of collagenase expression by either exogenous or endogenous IL-1. Furthermore, while freshly isolated fibroblasts cannot express IL-1 alpha they can express SAA3, and this autocrine mediator acts independently of IL-1 alpha to control the low level of collagenase expression that can be stimulated by PMA. These results provide further evidence for a newly emerging paradigm of collagenase regulation which emphasizes the requirement for extracellular routing of signals. They also suggest that SAA3 might be utilized independently of IL-1 alpha to control tissue remodeling in vivo.

The wound healing response following surgical injury to the cornea can be quite variable and difficult to predict. The goal of this paper is to elucidate basic mechanisms which control activation of the corneal stromal cell to the repair phenotype and its subsequent competence to mediate repair tissue remodeling. These studies focused on expression of the matrix metalloproteinase, collagenase. The experiments performed in this study lead to the proposal of a new paradigm for understanding the modulation of repair gene expression by the wound environment, that is, regulation through autocrine cytokine intermediates. This model suggests a novel point at which drug intervention can be used to alter the repair process.

IT has been observed that in the study of patients hospitalized for investigation of liver or gall-bladder disease, or both, studies of bromsulfalein excretion and cholecystography are often done concomitantly. In the usual manner this implies the administration of an iodine dye for the cholecystogram on the night before x-ray studies and the addition of a bromine-containing compound (bromsulfalein) on the next morning. On a number of occasions we have noted that the bromsulfalein retention measured in this fashion is frequently out of proportion to existing liver disease, and with repeated determinations at a later date, the values have shown . . .