Local control of α1-proteinase inhibitor levels:: regulation of α1-proteinase inhibitor in the human cornea by growth factors and cytokines

Alpha 1-proteinase inhibitor is a major serine proteinase inhibitor in the human cornea involved in the protection of the avascular corneal tissue against proteolytic damage. This inhibitor is upregulated systemically during infection, inflammation and injury. Cytokines that mediate the acute phase response such as IL-1 beta and IL-2 increased alpha 1-proteinase inhibitor present in corneal organ culture media. This released inhibitor represented mainly newly synthesized protein. However, IL-6, a general inducer of the acute phase response that upregulates alpha 1-proteinase inhibitor in all other tissues and cells tested, failed to alter corneal alpha 1-proteinase inhibitor levels over the tested period of 24 h. In addition to IL-1 beta and IL-2, alpha 1-proteinase inhibitor levels in the corneal organ culture medium increased following the addition of FGF-2 and IGF-1. The effect of the above growth factors and cytokines was relatively fast with maximal induction observed within the first 5 h. Among the tested growth factors and cytokines, IL-1 beta was the most potent and increased total corneal alpha 1-proteinase inhibitor levels approximately 2.4-fold in the comea organ culture medium. Newly, synthesized alpha 1-proteinase secreted into the medium increased 3.9-fold. In addition to the effect on corneal alpha 1-proteinase inhibitor, IL-1 beta also increased the amount of alpha 1-proteinase inhibitor released by monocytes and macrophages but not by HepG2, CaCo2, and MCF-7 cells within 24 h. These results suggest that the cornea can locally control levels of alpha 1-proteinase inhibitor in response to an inflammatory insult. (C) 1998 Elsevier Science B.V. All rights reserved.