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

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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 β and IL-2 increased α1-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 α1-proteinase inhibitor in all other tissues and cells tested, failed to alter corneal α1-proteinase inhibitor levels over the tested period of 24 h. In addition to IL-1 β and IL-2, α1-proteinase inhibitor levels in the corneal organ culture medium increased following the addition of FGF-2 and IGF-I. 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 β was the most potent and increased total corneal α1-proteinase inhibitor levels approximately 2.4-fold in the cornea organ culture medium. Newly, synthesized α1-proteinase secreted into the medium increased 3.9-fold. In addition to the effect on corneal α1-proteinase inhibitor, IL-1 β also increased the amount of α1-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 α1-proteinase inhibitor in response to an inflammatory insult.