LOCAL-CONTROL OF ALPHA-1-PROTEINASE INHIBITOR LEVELS - REGULATION OF ALPHA-1-PROTEINASE INHIBITOR IN THE HUMAN CORNEA BY GROWTH-FACTORS ANDCYTOKINES

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 syste mically during infection, inflammation and injury. Cytokines that medi ate the acute phase response such as IL-1 beta and IL-2 increased alph a 1-proteinase inhibitor present in corneal organ culture media. This released inhibitor represented mainly newly synthesized protein. Howev er, IL-6, a general inducer of the acute phase response that upregulat es 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-prot einase inhibitor levels in the corneal organ culture medium increased following the addition of FGF-2 and IGF-1. The effect of the above gro wth factors and cytokines was relatively fast with maximal induction o bserved within the first 5 h. Among the tested growth factors and cyto kines, IL-1 beta was the most potent and increased total corneal alpha 1-proteinase inhibitor levels approximately 2.4-fold in the comea org an culture medium. Newly, synthesized alpha 1-proteinase secreted into the medium increased 3.9-fold. In addition to the effect on corneal a lpha 1-proteinase inhibitor, IL-1 beta also increased the amount of al pha 1-proteinase inhibitor released by monocytes and macrophages but n ot by HepG2, CaCo2, and MCF-7 cells within 24 h. These results suggest that the cornea can locally control levels of alpha 1-proteinase inhi bitor in response to an inflammatory insult. (C) 1998 Elsevier Science B.V. All rights reserved.