Conversion of proepithelin to epithelins: Roles of SLPI and elastase in host defense and wound repair Journal Article
| Authors: | Zhu, J.; Nathan, C.; Jin, W.; Sim, D.; Ashcroft, G. S.; Wahl, S. M.; Lacomis, L.; Erdjument-Bromage, H.; Tempst, P.; Wright, C. D.; Ding, A. |
| Article Title: | Conversion of proepithelin to epithelins: Roles of SLPI and elastase in host defense and wound repair |
| Abstract: | Increased leukocyte elastase activity in mice lacking secretory leukocyte protease inhibitor (SLPI) leads to impaired wound healing due to enhanced activity of TGFβ and perhaps additional mechanisms. Proepithelin (PEPI), an epithelial growth factor, can be converted to epithelins (EPIs) in vivo by unknown mechanisms with unknown consequences. We found that PEPI and EPIs exert opposing activities. EPIs inhibit the growth of epithelial cells but induce them to secrete the neutrophil attractant IL-8, while PEPI blocks neutrophil activation by tumor necrosis factor, preventing release of oxidants and proteases. SLPI and PEPI form complexes, preventing elastase from converting PEPI to EPIs. Supplying PEPI corrects the wound-healing defect in SLPI null mice. Thus, SLPI/elastase act via PEPI/EPIs to operate a switch at the interface between innate immunity and wound healing. |
| Keywords: | controlled study; intercellular signaling peptides and proteins; unclassified drug; human cell; review; nonhuman; protein function; proteins; animal cell; mouse; animals; mice; animal tissue; complex formation; models, biological; cell growth; oxygen; interleukin 8; cell line; animal experiment; animal model; protein; dose-response relationship, drug; transfection; cos cells; phosphorylation; animalia; wound healing; blotting, western; amino acid sequence; molecular sequence data; interleukin-8; recombinant proteins; cell membrane; epithelium cell; epithelial cells; neutrophils; protein-tyrosine kinases; proteinase; immunity; host resistance; growth factor; enzyme release; tumor necrosis factor; two-hybrid system techniques; mice, inbred c3h; protein precursors; fungal proteins; growth inhibitors; leukocytes; pancreatic elastase; leukocyte activation; oxidizing agent; precipitin tests; focal adhesion kinase 2; humans; human; male; female; priority journal; secretory leukocyte proteinase inhibitor; leukocyte elastase; epithelin; progranulin; proteinase inhibitory proteins, secretory; secretory leukocyte peptidase inhibitor |
| Journal Title: | Cell |
| Volume: | 111 |
| Issue: | 6 |
| ISSN: | 0092-8674 |
| Publisher: | Cell Press |
| Date Published: | 2002-12-13 |
| Start Page: | 867 |
| End Page: | 878 |
| Language: | English |
| DOI: | 10.1016/s0092-8674(02)01141-8 |
| PUBMED: | 12526812 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 14 November 2014 -- Source: Scopus |
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