Human
extracellular ribonucleases (RNases) are widely distributed in various organs and body fluids and together with other members of the mammalian RNase A superfamily. In addition to their RNase activity, several RNases have been shown to have special biological actions, i.e., antitumor, antiviral and angiogenic properties. However, the molecular mechanisms of such activities are unclear. Using
protein microarrays amplified rolling circle amplification (RCA), we investigated the effects of EDN (Rnase 2), ECP (Rnase 3) and RNase 1 on leukocytes
cytokine production. We measured the levels of 78 different cytokines and growth factors in culture supernatants to determine the
cytokine profiles of cells treated with different combinations of RNases and RNase inhibitors. Members of human
ribonuclease family (such as Rnase 1, hEDN (Rnase 2) and Rnase 3) induced expression of certain sets of cytokines in human leukocytes, including ENA-78, EOT2, BLC, GDNF, 1309, IFN-alpha, IFN-gamma, IL-10, IL-12P40, IL-12p70, IL-13, IL-16, IL-18, IL-1beta, IL-1ra, IL-2Sra, IL-3, IL-6, IL-6sR, IL-7, IL-8, IP-10, MCP-1, MCP-2, MCP-3, MCSF, MIG, MDC, MIP-1alpha, MIP-1beta, MPIF-1,
NAP-2, RANTES, sCD23, OSM, TARC, TNF-alpha, TNF-R1 and uPAR. Thus members of the Rnase superfamily are therapeutic targets for treatment of inflammatory diseases and clinical conditions. Inhibition or augmentation of Rnase expression is used to modulate the
immune system and is beneficial for host defense against various diseases and is exploited as an
adjuvant. The expression of Rnases is a
diagnostic marker for
inflammation related conditions and is used to determine various
disease stages. In addition, expression of cytokines, chemokines, growth factors is used to monitor
efficacy of Rnase-base therapies.