Multifaceted roles of human elafin and secretory leukocyte proteinase inhibitor (SLPI), two serine protease inhibitors of the chelonianin family.
Elafin and SLPI are low-molecular weight proteins that were first identified as protease inhibitors in mucous fluids including lung secretions, where they help control excessive proteolysis due to neutrophil serine proteases (elastase, proteinase 3 and cathepsin G). Elafin and SLPI are structurally related in that both have a fold with a four-disulfide core or whey acidic protein (WAP) domain responsible for inhibiting proteases. Elafin is derived from a precursor, trappin-2 or pre-elafin, by proteolysis. Trappin-2, which is itself a protease inhibitor, has a unique N-terminal domain that enables it to become cross-linked to extracellular matrix proteins by transglutaminase(s). SLPI and elafin/trappin-2 are attractive candidates as therapeutic molecules for inhibiting neutrophil serine proteases in inflammatory lung diseases. Hence, they have become the WAP proteins most studied over the last decade. This review focuses on recent findings revealing that SLPI and elafin/trappin-2 have many biological functions as diverse as anti-bacterial, anti-fungal, anti-viral, anti-inflammatory and immuno-modulatory functions, in addition to their well-recognized role as protease inhibitors.
Moreau
Thierry
T
INSERM U618 Protéases et Vectorisation Pulmonaires, IFR 135 Imagerie fonctionnelle, Université François Rabelais, Tours, France. thierry.moreau@univ-tours.fr
Baranger
Kévin
K
Dadé
Sébastien
S
Dallet-Choisy
Sandrine
S
Guyot
Nicolas
N
Zani
Marie-Louise
ML
D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000494:pharmacology; D000890:Anti-Infective Agents / Q000494:pharmacology; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D053492:Elafin / Q000737:chemistry / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D008171:Lung Diseases / Q000188:drug therapy; D008969:Molecular Sequence Data; D053481:Secretory Leukocyte Peptidase Inhibitor / Q000737:chemistry / Q000494:pharmacology / Q000502:physiology*; D011503:Transglutaminases / Q000378:metabolism
D019380:Anti-HIV Agents; D000890:Anti-Infective Agents; D000893:Anti-Inflammatory Agents; D053492:Elafin; C506806:PI3 protein, human; C506814:SLPI protein, human; D053481:Secretory Leukocyte Peptidase Inhibitor; D011503:Transglutaminases