Arg-Gly-Asp-Ser is an integrin-binding sequence that inhibits integrin receptor function, thereby decreasing systemic inflammation by inhibiting collagen-triggered activation of leukocytes and attenuating the expression of inflammatory cytokines, MMP-9, and iNOS.

The Arg-Gly-Asp-Ser-modified surface up-regulates αvβ3 integrin and completely abolishes apoptosis induced by staurosporine, the Ca2+·Pi ion pair, and sodium nitroprusside upon attachment. The resistance to apoptosis, dependent on Arg-Gly-Asp-Ser, is eliminated when the phosphatidylinositol 3-kinase pathway is inhibited [1]. Arg-Gly-Asp-Ser interacts with survivin and procaspase-3, -8, and -9, with specific, high-affinity binding (Kd: 27.5 μM) to the C-terminus of survivin [4].

Administering Arg-Gly-Asp-Ser at doses of 2.5 or 5 mg/kg, one hour before lipopolysaccharide (LPS), significantly inhibits LPS-induced matrix metallopeptidase-9 (MMP-9) activity in bronchoalveolar lavage (BAL) fluid four hours after LPS exposure. Similarly, Arg-Gly-Asp-Ser given intraperitoneally (i.p.) at doses of 1, 2.5, or 5 mg/kg, one hour before LPS, effectively suppressed the LPS-induced increases in tumor necrosis factor-alpha (TNF-α) and macrophage inflammatory protein (MIP)-2 levels in BAL fluid at the four-hour mark post-LPS [2]. Furthermore, the Arg-Gly-Asp-Ser peptide significantly lowers TNF-α and MIP-2 production and reduces myeloperoxidase (MPO) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activity [3].