Uteroglobin, a possible ligand of the lipoxin receptor inhibits serum amyloid A-driven inflammation.
Serum amyloid A (SAA) production is increased by inflamed arthritic synovial tissue, where it acts as a cytokine/chemoattractant for inflammatory and immune cells and as an inducer of matrix degrading enzymes. SAA has been shown to bind lipoxin A4 receptor, a member of the formyl-peptide related 2 G-protein coupled receptor family (ALX) and elicit proinflammatory activities in human primary fibroblast-like synoviocytes (FLS). We report on the identification of uteroglobin, a small globular protein with potent anti-inflammatory activities, as a possible ligand of ALX. Uteroglobin-specific association with ALX was demonstrated by an enzyme immunoassay experiment employing a cell line engineered to express the human ALX receptor. Uteroglobin's interaction with ALX resulted in the inhibition of SAA responses, such as attenuation of phospholipase A2 activation and cellular chemotaxis. In FLS, uteroglobin showed an antagonism against SAA-induced interleukin-8 release and decreased cell migration. These novel roles described for uteroglobin via ALX may help elucidate genetic and clinical observations indicating that a polymorphism in the uteroglobin promoter is linked to disease outcome, specifically prediction of bone erosion in patients with rheumatoid arthritis or severity of IgA glomerulonephritis and sarcoidosis.
Astellas Pharma US, Northbrook, IL 60062, USA.
Giovanni
G
Antico
Advocate Christ Medical Center & Hope Children's Hospital, 4440 W 95th Street Oak Lawn, IL 60453, USA.
Monica
M
Aloman
Department of Rheumatology, University Medical Center-Ljubljana, 1000 Ljubljana, Slovenia.
Katja
0000-0002-8062-7908
K
Lakota
Departments of Medicine, Pharmacology, Biochemistry and Radiation Oncology, The University of Mississippi Medical Center, Cancer Institute, Jackson, MS 39216, USA.
Lucio
L
Miele
Sanofi-Aventis, Bridgewater Township, NJ 08807, USA.
Stefano
S
Fiore
Department of Rheumatology, University Medical Center-Ljubljana, 1000 Ljubljana, Slovenia ; Faculty of Mathematics, Natural Science and Information Technology, University of Primorska, 6000 Koper, Slovenia.
Snezna
S
Sodin-Semrl
D000818:Animals; D016466:CHO Cells; D002465:Cell Movement; D002633:Chemotaxis; D003412:Cricetulus; D004717:Endometrium / Q000166:cytology; D005260:Female; D005347:Fibroblasts / Q000166:cytology; D018922:HL-60 Cells; D006801:Humans; D007124:Immunoenzyme Techniques; D007249:Inflammation; D008024:Ligands; D054467:Phospholipases A2 / Q000378:metabolism; D011401:Promoter Regions, Genetic; D044067:Receptors, Lipoxin / Q000378:metabolism*; D000685:Serum Amyloid A Protein / Q000378:metabolism*; D013583:Synovial Membrane / Q000166:cytology; D014598:Uteroglobin / Q000378:metabolism*
D008024:Ligands; D044067:Receptors, Lipoxin; C556389:SCGB1A1 protein, human; D000685:Serum Amyloid A Protein; D014598:Uteroglobin; D054467:Phospholipases A2