SLPI and elafin: one glove, many fingers

Abstract

Elafin and SLPI (secretory leucocyte protease inhibitor) have multiple important roles both in normal homoeostasis and at sites of inflammation. These include antiprotease and antimicrobial activity as well as modulation of the response to LPS (lipopolysaccharide) stimulation. Elafin and SLPI are members of larger families of proteins secreted predominantly at mucosal sites, and have been shown to be modulated in multiple pathological conditions. We believe that elafin and SLPI are important molecules in the controlled functioning of the innate immune system, and may have further importance in the integration of this system with the adaptive immune response. Recent interest has focused on the influence of inflamed tissues on the recruitment and phenotypic modulation of cells of the adaptive immune system and, indeed, the local production of elafin and SLPI indicate that they are ideally placed in this regard. Functionally related proteins, such as the defensins and cathelicidins, have been shown to have direct effects upon dendritic cells with potential alteration of their phenotype towards type I or II immune responses. This review addresses the multiple functions of elafin and SLPI in the inflammatory response and discusses further their roles in the development of the adaptive immune response.

Characterization of Trichuris muris secreted proteins and extracellular vesicles provides new insights into host–parasite communication

“…Protease inhibitors (particularly serine protease inhibitors and secretory leukocyte proteinase inhibitor (SLPI)-like proteins – proteins containing mostly WAP domains) are abundantly represented in the T. muris genome [8]. SLPI-like proteins have been suggested to have immunomodulatory properties as well as a role in wound healing [8,46–48], so they could be secreted in an attempt to modulate the host’s immune response and repair damage caused by both feeding/migrating worms and immunopathogenesis. In addition, we found five SCP/TAPS (also known as CAP-domain) proteins.…”

Promotive role of recombinant HE4 protein in proliferation and carboplatin resistance in ovarian cancer cells

“…The HE4 gene resides on human chromosome 20q12-13.1, a region that harbors a locus of 14 genes encoding protein domains that have homology with whey acidic protein (WAP) (3). Two functions attributed to this family of proteins are the regulation of proinflammatory mediators and anti-bacterial or anti-fungal activity (4,5). There is a growing body of evidence demonstrating the tumorpromoting roles of WAP domain family members (6,7).…”

SLPI (secretory leukocyte peptidase inhibitor)

“…The WAPs domains of the molecule are involved, and this is due to cationic residues that allow the disruption of the membranes of target organisms (Verma et al 2007;Gomez et al 2009;Nishimura et al 2008). The antimicrobial activity of human SLPI has been described for various bacteria such as Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus epidermis (Wiedow et al 1998;Wingens et al 1998), Mycobacterium tuberculosis (Gomez et al 2009), and Escherichia coli (Williams et al 2006). Therefore this activity is against Gram negative and Gram positive bacteria and is part of the defense system of the mucosa.…”

“…Antiprotease activity: The inhibition of protease activity was described for C-terminus domain against elastasa, cathepsin G, trypsin, chymotrypsin, tryptase and chymase (Williams et al 2006). Thus, SLPI major function is inhibit inflammation by blocking the proteolytic activity of serine proteinases released by leukocytes and also through blocking the LPS effects, such as the upregulation of several cytokines like TNFalpha, MCP-1 and IL-6 (Yang et al 2005;Jin et al 1998;Taggart et al 2005;Ashcroft et al 2000).…”