Faculty Collaboration Database

Local control of alpha1-proteinase inhibitor levels: regulation of alpha1-proteinase inhibitor in the human cornea by growth factors and cytokines. Biochim Biophys Acta 1998 May 27;1403(1):37-46

Date

06/12/1998

Pubmed ID

9622589

DOI

10.1016/s0167-4889(98)00018-4

Scopus ID

2-s2.0-0032571944 (requires institutional sign-in at Scopus site)   45 Citations

Abstract

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-1beta and IL-2 increased alpha1-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 alpha1-proteinase inhibitor in all other tissues and cells tested, failed to alter corneal alpha1-proteinase inhibitor levels over the tested period of 24 h. In addition to IL-1beta and IL-2, alpha1-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-1beta was the most potent and increased total corneal alpha1-proteinase inhibitor levels approximately 2.4-fold in the cornea organ culture medium. Newly, synthesized alpha1-proteinase secreted into the medium increased 3.9-fold. In addition to the effect on corneal alpha1-proteinase inhibitor, IL-1beta also increased the amount of alpha1-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 alpha1-proteinase inhibitor in response to an inflammatory insult.

Author List

Bosković G, Twining SS

Author

Sally Twining PhD, MA Emeritus Professor in the Biochemistry department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Caco-2 Cells
Cornea
Epidermal Growth Factor
Fibroblast Growth Factor 2
Growth Substances
Humans
Insulin-Like Growth Factor I
Interleukin-1
Interleukin-2
Interleukin-6
Organ Culture Techniques
Transforming Growth Factor alpha
Tumor Cells, Cultured
Tumor Necrosis Factor-alpha
alpha 1-Antitrypsin