New insights into ADAMs regulation of the GRO-α/CXCR2 system: focus on Sjögren's syndrome.
Chemokine-dependent signaling in immune cells is a very important mechanism leading to integrin activation and leukocyte recruitment. During the last years, several studies were performed investigating the role of the chemokine Growth-related oncogene-alpha (GRO-α) and its receptor CXC chemokine receptor 2 (CXCR2) in different diseases. Recently, many new functions and properties of GRO-α/CXCR2 system have been discovered and associated with atherosclerosis, angiogenesis, and many inflammatory conditions, such as autoimmune diseases. The purpose of this review is to discuss current advances in our understanding of the function of the GRO-α/CXCR2 system and related clinical implications associated with autoimmune diseases, such as primary Sjogren's syndrome (pSjS). Included is a discussion of the role of the ADAM17 metalloproteinase in modulating the GRO-α/CXCR2 axis in pSjS. Notably inhibitors of ADAM17 are being developed for the treatment of various autoimmune diseases. We hope to further evaluate this system in the pathogenesis of autoimmune diseases to promote a background for therapeutic interventions.
a Department of Basic Medical Sciences, Neurosciences and Sense Organs, Section of Human Anatomy and Histology, Laboratory of Cell Biology , University of Bari Medical School , Bari , Italy.
Margherita
M
Sisto
a Department of Basic Medical Sciences, Neurosciences and Sense Organs, Section of Human Anatomy and Histology, Laboratory of Cell Biology , University of Bari Medical School , Bari , Italy.
Sabrina
S
Lisi
D051722:ADAM Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000072198:ADAM17 Protein; D000818:Animals; D015551:Autoimmunity; D054360:Chemokine CXCL1 / Q000235:genetics / Q000378:metabolism*; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D019483:Disintegrins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D005810:Multigene Family; D011485:Protein Binding; D023063:Receptors, Interleukin-8B / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012859:Sjogren's Syndrome / Q000175:diagnosis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D013329:Structure-Activity Relationship
D054360:Chemokine CXCL1; D018925:Chemokines; D019483:Disintegrins; D023063:Receptors, Interleukin-8B; D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human
ADAM 17; CXCR2; GRO-α; Sjögren′s syndrome; autoimmune diseases